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- Effect of lupeol on testicular lesions induced by cadmium chloride in rats
Abstract: Objective: Heavy metals and environmental pollutants, such as cadmium chloride, congenital disorders, and certain diseases, can lead to infertility in men. In this study, the effects of lupeol (an active pentacyclic triterpenoid with antioxidant properties) on testicular injuries induced by cadmium chloride were investigated in male rats.Materials and Methods: Lupeol was obtained from Sigma-Aldrich, and the experiment included 40 male Wistar rats divided into 8 groups (healthy control, healthy rats treated with 100, 200, and 400 mg/kg of lupeol, cadmium chloride, and three groups that received cadmium chloride and were treated with 100, 200, and 400 mg/kg of lupeol). After oral treatment, rats were anesthetized, and blood and testicular tissue sampling was done. Subsequent analysis of oxidative stress enzymes, such as malondialdehyde (MDA) and superoxide dismutase (SOD), testosterone, sperm motility, and Aquaporin 9 (AQ9) levels was performed using ELISA, histopathology, and immunohistochemistry techniques, respectively. Immunohistochemistry staining was done for expression of Aquaporin 9 in seminiferous tubules.Results: The results showed that compared to the healthy control, cadmium chloride caused a significant decrease in SOD, testosterone, sperm motility, and sperm vitality, with severe destruction of spermatogenic tubes and a significant increase in MDA and AQ9 rate. Rats which were treated with cadmium chloride+400 mg/kg of lupeol showed a significant increase in SOD, testosterone, histopathology, sperm motility, and sperm vitality rate, and significant organization of spermatogenic tubes in testis tissue. There was also a decrease in MDA and AQ9 of rats that received high-dose lupeol. (P<0.001)Conclusion: This study suggests that lupeol has a high potential for improving male reproduction and antioxidants in rats exposed to oxidative stress.
- The adjuvant therapy of edible herbal product including colchicum bulb,
olive leaf, black cumin seeds, lavender flower, and ginger rhizome on the
outcome of patients with severe and critical COVID-19: A double-blind
randomized controlled clinical trial
Abstract: Objective: The present study aimed at evaluating the effect of combination of medicinal plants, including Colchicum autumnal L., Olea europaea L., Nigella sativa L., Lavandula angustifolia L., and Zingiber officinale Roscoe, on the recovery and outcome of COVID-19 patients.
Materials and Methods: This study was conducted on 150 COVID-19 patients. All patients received both pharmaceutical and supportive treatments. In addition to the standard care treatment, intervention group received two capsules of herbal medicine orally every 8 hours, while control group received placebo.
Results: Oxygen saturation percentage (SpO2) of the intervention group (median:88.00) was significantly higher than that of the control group (median:86.00), while C-reactive protein (CRP) of the intervention group (median:20.00) was significantly lower than that of the control group (median:28.00) at the time of hospital discharge (p<0.05).
Conclusion: The combination of studied medicinal plants could significantly reduce the oxygen requirement and oxygen therapy.
- The protective properties of resveratrol against glycerol-induced acute
kidney injury in rats
Abstract: Objective: After rhabdomyolysis, muscle tissue releases substances such as myoglobin, creatine kinase, and electrolytes into the bloodstream, potentially leading to acute kidney injury (AKI). Resveratrol (RSV) is a polyphenol compound with anti-inflammatory and antioxidant effects and it is found in various plants. This research evaluated the protective effects of RSV in rhabdomyolysis-induced AKI in rat kidneys.
Materials and Methods: Thirty-six male Wistar rats were randomly assigned to six groups (n=6): 1) control (normal saline), 2) glycerol only (10 ml/kg, intramuscular), 3, 4, and 5) glycerol +RSV (5, 10, and 25 mg/kg, intraperitoneal injection) and 6) RSV (25 mg/kg). After 4 days, pathological alterations and the level of blood urea nitrogen (BUN) and serum creatinine were determined. Malondialdehyde (MDA), glutathione (GSH), neutrophil gelatinase-associated lipocalin (NGAL), and tumor necrosis factor-α (TNF-α) proteins were investigated in rat kidneys.
Results: Injection of 50% glycerol (10 ml/kg, IM) resulted in pathological lesions, elevated levels of MDA (p<0.001), BUN (p<0.01), serum creatinine (p<0.001), TNF-α (p<0.01), and NGAL protein (p<0.001), and decreased GSH content (p<0.001) compared to the control animals. These findings indicated AKI induced by rhabdomyolysis. RSV (25 mg/kg) administration significantly decreased serum creatinine, BUN, MDA, NGAL, and TNF-α levels compared to the glycerol group. Histopathologically, tubule necrosis, myoglobin cast formation and glomerular atrophy increased in the glycerol group and reduced in animals that received RSV.
Conclusion: In the glycerol-induced AKI rat model, RSV administration alleviated renal dysfunction by reducing oxidative stress and inflammatory responses.
- Anti-cancer effects of frankincense methanolic extract on brain metastatic
breast cancer cells
Abstract: Objective: Brain metastasis in patients with breast cancer is considered a deadly event. The oleogum resins of Boswellia species, known as Frankincense has been found to have anti-cancer properties in many studies. The main purpose of our research was to evaluate these effects on brain metastatic cancer cells.
Materials and Methods: Primary (4T1T) and brain metastatic (4T1B) tumor cells were isolated from breast cancerous mice. Cytotoxic, apoptotic, and anti-metastatic effects of the methanolic extract of frankincense were evaluated with MTT assay, propidium iodide (PI) flow cytometric assay, and scratch test, respectively. Zymography assay was used to evaluate the effects of extract on the matrix metalloproteinases-2 and -9 (MMP-2 /9) expression/activity.
Results: The methanolic extract of frankincense has significant cytotoxic and apoptotic effects on 4T1B cells (p<0.001). Interestingly, 4T1B cells are more prone to these effects than 4T1T cells. In 4T1B, the anti-metastatic effects of frankincense extract were confirmed. Frankincense suppressed MMP-2/9 protein expression both in 4T1T and 4T1B.
Conclusion: Our findings indicated that frankincense extract has a potent cytotoxic effect on brain metastatic tumor cells and induces apoptosis in these cells. Unlike many anti-cancer drugs which have very little ability to combat and kill brain metastatic cancer cells, frankincense extract can be considered a suitable candidate to fight these cells.
- Apoptotic and anti-migratory activity of Citrus limon rind essential oil
encapsulated in niosome against human breast cancer cells
Abstract: Objective: This study aimed to formulate Citrus limon fruit rind’s essential oil (EO) and to analyze its impact on breast cancer cells.
Materials and Methods: Initially, the cytotoxicity of EO (0.09-9 µg/ml) and doxorubicin (0.5-5 µM) on MCF-7, SK-BR-3, and MDA-MB-231 breast cancer cells was assessed using the MTT assay following 24-72 hr treatment. The cells were then treated with niosomes containing 4.5 µg/ml EO and 0.5 µM doxorubicin for 48 hr. Flow cytometry, migration assay, and RT-qPCR were used to study the cell behavior.
Results: MTT results indicated that both EO and doxorubicin alone exhibited severe cytotoxicity (viability ≤ 30%) towards all three cells after 48 hr . When treated with encapsulated EO, the apoptotic death rate in MCF-7, MDA-MB-231, and SK-BR-3 cells was substantially diminished to 14%, 28%, and 9%, respectively. Similarly, encapsulated doxorubicin induced mild apoptotic death in these cells. Encapsulated EO and doxorubicin significantly prevented the migration of all cells. Following treatment with the encapsulated EO, a notable reduction in the expression of VIM, SLUG, SNAIL, and JUN, which are promoters of cancer cell invasion, was seen. Conversely, the expression of the FAS receptor, an active participant in the extrinsic apoptosis pathway, increased (p˂0.01).
Conclusion: Lemon EO has apoptotic and anti-migratory effects on breast cancer cells, comparable to that of doxorubicin. Utilizing niosome as an efficient delivery modality effectively mitigates the adverse effects of EO and can be used for in vivo delivery of it to cancer cells.
- The protective effects of Allium ampeloprasum Subsp Iranicum on
cyclophosphamide-induced immunosuppression in NMRI Mice: A promising
natural immunomodulator
Abstract: Objective: Cyclophosphamide (CTX) is an effective anticancer drug, but toxic effects against normal human tissues are its dose-limiting drawback. The aim of this research was to investigate the in vivo immunomodulatory activities of Allium ampeloprasum Subsp Iranicum against CTX-induced toxicity in mice.
Materials and Methods: Extract of the whole plant of A. ampeloprasum Subsp Iranicum was obtained using the maceration technique, and its total phenolic and flavonoid contents were quantified through spectrophotometric analysis. Mice received daily oral administration (PO) of the extract (150 mg/kg) for a duration of 14 days, either as a standalone treatment or in conjunction with an intraperitoneal (IP) injection of 20 mg/kg CTX. The effects of the extract on body weight, spleen weight, white blood cell (WBC), serum antibody titer hemagglutination (HA), delayed-type hypersensitivity response (DTH), lymphocyte proliferation, cytokine production, and histopathological examinations were evaluated.
Results: A. ampeloprasum Subsp Iranicum restored several parameters including spleen weight (p<0.001), WBC (p<0.001), lymphocytes (p<0.05), and monocytes (p<0.01), HA titer (p<0.05), and DTH response (p<0.01). A. ampeloprasum Subsp Iranicum notably stimulated lymphocyte proliferation to PHA (p<0.01) and LPS (p<0.05) and recovered interferon (IFN)-γ (p<0.001) and interleukin (IL)-4 (p<0.001) levels in the immunosuppressed mice. Also, CTX-induced histopathological changes were reversed by A. ampeloprasum Subsp Iranicum.
Conclusion: Analyses revealed A. ampeloprasum Subsp Iranicum could regulate immunity and increase host immune responses. The observed strengthening effect can be attributed to the high amount of flavonoids and dipropyl trisulfide compounds present in A. ampeloprasum Subsp Iranicum.
- Fertility-enhancing effects of Prunus amygdalas oil on reproductive
functions of male rats: A two-generation study
Abstract: Objective: Prunus amygdalas (Almond; PA) has extensively been used in traditional medicine and has been the source of robust phenolic compounds. The current study intended to evaluate the fertility-enhancing effect of PA on male rats infertility and reproductive performance of two successive generations of rats namely, F0 and F1.
Materials and Methods: Chemical composition of the oil was established with the aid of Gas Chromatography-Mass Spectrometry (GC-MS). The oil was then subjected to in-vitro antioxidant assay via DPPH (1,1-diphenyl-2-picrylhydrazyl) and ROS (reactive oxygen species), followed by in vivo toxicity testing. In the fertility assessment, 1 and 2 ml/kg of PA oil was given to rats up to pre-cohabitation, cohabitation, gestation and lactation period. The reproductive performance along with hormonal and antioxidant markers of F1 generationwas estimated and histopathological evaluation of both sex organs was done. Further, ethanol-induced male infertility model was established and sex hormones, antioxidant markers (superoxide dismutase (SOD), Glutathione peroxidase (GPx) and lipid profile were assessed along with histopathology of male sex organs.
Results: The PA oil supplementation showed pronounced fertility outcomes in terms of raised litter size, sex hormones and antioxidant markers in both generations. Moreover, in ethanol-induced male infertility model, PA oil significantly restored sex hormones, ROS and GPx levels. Histological findings also endorsed better spermatogenesis with enhanced architecture.
Conclusion: These results strongly suggest that PA oil rich in PUFA (poly-unsaturated fatty acids) might be a promising treatment option in future for male/female sterility.
- Perillyl alcohol, quercetin, and berberine combination therapy ameliorates
experimental pulmonary arterial hypertension: Effects on the lung miR-204
expression, remodeling, and inflammatory factors
Abstract: Objective: Pulmonary artery hypertension (PAH) is a devastating syndrome. Our previous studies showed that perillyl alcohol (P), berberine (B) and quercetin (Q) improve PAH. In this study, we investigated the effects of sub-effective doses of these derivatives in double and triple combination forms on PAH in rats.
Materials and Methods: Forty nine rats were divided into seven groups (n=7): 1) control, 2) monocrotaline (MCT), 3) MCT+vehicle (veh), 4) MCT+BP, 5) MCT+PQ, 6) MCT+BQ, and 7) MCT+BPQ. After three weeks of PAH induction with MCT (60 mg/kg), either vehicle (ethanol 5% in saline) or one of the above combinations (dose of 20 mg/kg for B, and doses of 20 and 10 mg/ kg for P and Q in vehicle) was administered for three weeks. Right ventricular (RV) pressure, contractility indices, lung pathology, miR-204 expression, oxidative stress markers, inflammation and apoptosis were assayed.
Results: MCT increased RV systolic pressure and hypertrophy, and lung arteriole wall thickness, fibrosis and leukocyte infiltration in the MCT group compared to the CTL group. All treatments improved these effects significantly. Furthermore, MCT reduced antioxidant factors, Bax, P21 and miR-204 expression and increased Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 (IL-6) and Bcl-2. All of these effects were recovered by combination treatments.
Conclusion: The results showed that combination therapy with sub-effective/ineffective doses of these compounds had ameliorative effects against PAH.
- Examining efficacy and safety of ethyl acetate extract from Allium
hirtifolium as complementary therapy in COVID-19: A randomized,
multicenter, controlled clinical trial
Abstract: Objective: Given the apparent life-threatening nature of COVID-19, finding an effective treatment is under investigation.
Materials and Methods: We assessed effect of shallomin oral syrup (co IranAmin®) as a complementary treatment to improve the clinical outcomes in COVID-19 patients. Patients in the control group received the approved treatment protocol (lopinavir/ritonavir), while those in the intervention group were treated with the oral syrup shallomin in addition to the approved treatment. Clinical status of treated patients was recorded and compared.
Results: There were meaningful differences between the two groups regarding shortened length of hospital stay and the recovery time for cough, myalgia, sore throat, and shortness of breath. No side effect occurred in the intervention group compared to the control group in terms of biochemical and hematological factors.
Conclusion: It seems that the treatment with shallomin syrup showed remarkable contribution to the recovery of COVID-19 induced symptoms in the patients under lopinavir/ritonavir therapy.
- Investigating the effect of zeaxanthin on olanzapine-induced metabolic
disorders in rats
Abstract: Objective: Olanzapine (OLZ) is used by some patients with bipolar disorder and schizophrenia. Some of its side effects include weight gain and metabolic syndrome. Zeaxanthin (Zx), a yellow pigment found in egg yolk as well as some yellow and orange plants and fruits, is an anti-obesity factor that aids in the treatment of metabolic disorders. The effects of Zx on metabolic disorders caused by OLZ were investigated in this study.
Materials and Methods: Female Wistar rats were randomly divided into seven groups (n=6): 1. control (vehicle); 2. OLZ (5 mg/kg, 14 days, intraperitoneal (i.p.)); 3-5. OLZ + Zx (12.5, 25, and 50 mg/kg, 14 days, gavage); 6. OLZ+ metformin (100 mg/kg, 14 days, i.p.); and 7. Zx (50 mg/kg, 14 days). Weight changes were checked every 3 days and food intake was monitored every day. Systolic blood pressure, insulin, blood sugar, triglyceride, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and leptin levels were evaluated on the last day of the study.
Results: OLZ caused an increase in weight (84.5% increase on day 15), food intake, blood pressure, triglyceride, LDL, insulin, blood sugar, and leptin compared to the control group (p<0.01 and p<0.001). The use of different doses of Zx (12.5, 25, and 50 mg/kg) and metformin decreased weight (the percentages of weigh reduction on day 15 were 91.92% for Zx (50 mg/kg) and 59.39% for metformin), food intake, systolic blood pressure, triglyceride, LDL, insulin, blood sugar, and leptin compared to the OLZ group. The amounts of cholesterol and HDL were not different in different groups.
Conclusion: Zx alleviates metabolic abnormalities including hypertension, hyperglycemia, and dyslipidemia in rats.
- The effect of evening primrose oil on adolescent girl patients with PCOS:
A double-blind placebo-controlled randomized study
Abstract: Objective: Polycystic ovary syndrome (PCOS) is a common disorder among women of reproductive age. The goal of the current study was to evaluate the effect of evening primrose oil (EPO) (Oenothera biennis) in adolescent girls with PCOS.
Materials and Methods: In the current double-blind and randomized controlled research, 76 patients completed the study in two groups (38 in the placebo and 38 in the EPO groups). The patients were asked to take oral placebo or EPO (1000 mg/day) for 12 weeks. Biochemical, clinical, and ultrasonography assessments were performed. The data was analyzed using SPSS statistical software.
Results: After the intervention, the regulation of the menstrual cycle in the EPO group was different from that of the placebo group (p=0.04). The levels of insulin, testosterone, and free androgen index (FAI) in the EPO group were lower than those of the placebo group (p<0.05). The sex hormone binding globulin (SHBG) levels in the EPO group were higher than those of the placebo group (p=0.01). While the number of immature follicles decreased in the EPO group, this difference was not statistically significant (p=0.8).
Conclusion: Overall, EPO administration for 12 weeks in young women with PCOS regulated the irregular menstrual cycle. In addition, the levels of insulin, testosterone, FAI, and SHBG changed. Therefore, EPO may be effective in improving hormonal and menstrual irregularities.
- Melissa officinalis extract improved high-fat-diet-induced anxiety-like
behaviors, depression, and memory impairment by regulation of serum BDNF
levels in rats
Abstract: Objective: Melissa officinalis (MO) hydroalcoholic extract has shown neuroprotective effects. We assess the possible therapeutic effects of Melissa officinalis extract (MOE) on blood biochemical and Brain-Derived Neurotrophic Factor (BDNF) levels as well as neurobehavioral consequences of high-fat-diet (HFD)-induced obese rats.
Materials and Methods: Eighty male Wistar rats weighing between 180 and 220 g were divided into two groups at the beginning of the experiment and fed with normal diet (ND) or HFD for 5 weeks. Then, each group was divided into four subgroups (10 rats in each group) and treated daily with MOE (50, 100, 150 mg/kg, intraperitoneal) or vehicle for another two weeks. At the end of the experiments, fasting blood glucose (FBG), blood lipid profile, and serum brain-derived neurotrophic factor (BDNF) levels were measured. The sucrose preference test (anhedonia and depression), open field test (locomotor), elevated plus maze (anxiety), Y-maze (working memory), and Morris water maze test (spatial memory) were done.
Results: Feeding with HFD for 7 weeks caused obesity, anhedonia, anxiety, depression and learning and memory disorders in rats and a decrease in serum BDNF level. Administration of MOE at 100 or 150 mg/kg to HFD-fed rats decreased weight gain, FBG, and serum levels of total low-density lipoprotein cholesterol and increased serum BDNF levels. It also improved changes in locomotor activity, anxiety, depression, and learning and memory in HFD-fed rats.
Conclusion: The results show that MOE has a therapeutic effect on model rats with HFD-induced metabolic and neurobehavioral abnormalities through regulation of BDNF secretion.
- Heracleum persicum L. extract protects gentamicin-induced testicular
toxicity
Abstract: Objective: The objective of this study was to assess the protective effects of Heracleum persicum L. leaves extract (HPE) against oxidative damage induced by gentamicin (GM) in the testes of rats through biochemical, histopathological, and immunohistochemical approaches.
Materials and Methods: Thirty-six male Wistar rats were divided into six groups (n=6/group) for 50 days. On day 51, the study assessed serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone (TT), as well as antioxidant enzyme activity, nitric oxide levels, and various parameters related to testicular tissue (including the ferric reducing ability of plasma (FRAP), thiol, and thiobarbituric acid reactive substances (TBARS) levels). The stereological indices of seminiferous tubules were measured using serial sections of testicular tissue stained with hematoxylin and eosin, while the apoptosis rate of testicular parenchymal cells (p53, Caspase-3, and Bcl-2 positive cells) was also determined.
Results: In the groups treated with HPE, particularly at 750 mg/kg, there was a significant increase (p<0.05) in LH, FSH, and TT hormone levels, an enhanced serum antioxidant enzyme activity and significantly reduced (p<0.05) nitric oxide levels. HPE inhibited the apoptotic pathway involving Bax/p53/Caspase-3 (significantly decreased (p<0.05) all three genes), thereby preserving the structure and function of the testicular tissue. Consequently, the number of p53 and Caspase-3 positive testicular cells decreased significantly (p<0.05), while the number of Bcl-2 positive cells increased.
Conclusion: HPE demonstrated potential in protecting the function and structure of testis against toxic and oxidative damages.
- Preparation and evaluation of hair growth promoting effect of
transferosomes containing red clover extract and caffeine alone or in
combination
Abstract: Objective: Trifolium pratense L. (Red clover) belongs to the Leguminosae family. This study was designed to develop transferosome formulations containing red clover extract or caffeine alone or in combination and evaluate their effects on hair growth in mice.
Materials and Methods: Thin-lipid film hydration technique was used to make transferosomes. Six groups (n=6) of male Swiss mice (28-32 g) were used. One group was normal control. The second group received transferosome without drug. Groups 3 to 5 received 100 µl of transferosomes containing red clover extract (1%) or caffeine (0.002%) alone or in combination. The sixth group received minoxidil (2%). Treatments continued six days per week for 3 weeks and each week, the hair growth scores were recorded. At the end, sections of the skin were prepared for determining the percent of follicles in the anagen phase.
Results: Encapsulation efficiency was 84.3, 81.6 and 89.1% for red clover, caffeine and red clover+caffeine transferosomes respectively. After 24 hr, the cumulative release of red clover and caffeine formulations was 77.6 and 76.9%, respectively. Treatments produced no significant change in hair growth after two weeks but at the end of the third week, all treatments significantly increased the hair growth and the effects were comparable with minoxidil. The combination of red clover and caffeine was not more effective than either alone.
Conclusion: Transferosome formulations of caffeine and red clover alone demonstrated hair growth effect but their combination had no additive effect which might be due to a physicochemical or pharmacodynamic interaction.
- Antimicrobial effectiveness of aqueous and alcoholic herbal extracts on
Streptococcus mutans: A systematic review and meta-analysis of randomized
controlled trials
Abstract: Objective: Debates about the efficacy of herbal products in oral care have inspired researchers to conduct a large number of trials. This systematic review and meta-analysis aimed to assess the antibacterial efficacy of aqueous and alcoholic herbal extracts against Streptococcus mutans (SM) as the main cariogenic microorganism.
Materials and Methods: Online databases PubMed, Scopus, Cochrane Library, Web of Science, and Magiran were searched for randomized controlled trials evaluating the efficacy of herbal products against SM published up to July 2023. Meta-analyses were performed for immediate and long-term effects based on random effect model.
Results: Out of 57 studies that met the selection criteria for systematic review, 26 were subjected to meta-analysis. Considering both immediate and long-term effects on salivary SM, aqueous and alcoholic herbal extracts were significantly superior in the reduction of SM over non-herbal agents (immediate: SMD = -1.16; 95%CI: -2.03, -0.29, long-term: SMD = -0.76; 95%CI: -1.35, -0.17). However, the difference was not significant in the reduction of SM of plaque (SMD = -0.30, 95%CI: -1.25, 0.65). The subgroup analyses showed no significant difference compared to chlorhexidine (p>0.05). The overall quality of evidence was considered low based on GRADE tool.
Conclusion: Current evidence suggests encouraging results for herbal extracts in reduction of SM, but not over chlorhexidine. However, there is still insufficient evidence to recommend them as the first option for oral care. High-quality randomized controlled trials are required to assert the safety and effectiveness of them for preventing dental caries.
- Cinnamon pretreatment modulates gene expression of tight junction proteins
in a rat model of stroke
Abstract: Objective: Brain ischemia generally results in irreversible brain damage or death. One of the most important features of an ischemic stroke is disruption of the Blood-brain barrier (BBB). In this study, we examined the effect of cinnamon hydroalcoholic extract consumption on BBB permeability and expression of some genes regulating its function.
Materials and Methods: Sixty male Wistar rats were divided into 5 groups; sham (high-fat diet+ sham surgery), Model (Middle Cerebral Artery Occlusion, MCAO+ high-fat diet), Lovastatin (high-fat diet + lovastatin + MCAO surgery), low and high dosage cinnamon (high-fat diet + cinnamon 130 or 260 mg, respectively+ MCAO surgery). The two doses of cinnamon (130 and 260 mg) were administered intraperitoneally. Twelve hours after ischemic stroke induction, brain right hemisphere tissues were collected and calpain I, calpainII, occludin and VEGF genes expression were quantified by Real-Time -PCR. Accordingly, p-selection protein levels were measured by ELISA method.
Results: Cinnamon hydroalcoholic extract reduced the BBB permeability compared with the model group (p<0.05). Stroke increased calpain and VEGF genes while decreased occludin gene expression (p<0.001). Conversely, cinnamon administration increased occludin gene expression while calpain and VEGF genes were down-regulated (p<0.01). Pretreatment with cinnamon significantly diminished the P-Selectin protein levels as compared with the model group dose dependently (p<0.001).
Conclusion: It seems that cinnamon restores BBB function by regulating the elements involved in its permeability.
- Effect of pretreatment with Devil's Claw on locomotor activity, infarct
volume, and neuronal density in focal cerebral ischemia in rats
Abstract: Objective: Stroke is a highly prevalent and devastating condition affecting millions worldwide. The Devil's Claw (DCW) plant is a native African plant whose anti-inflammatory, antioxidant, and neuroprotective properties have been investigated. We postulated that DCW could protect the brain injury caused by cerebral ischemia.
Materials and Methods: The rats were randomly divided into four groups. The sham and control (Ctrl) groups received pretreatment with a distilled water vehicle. Doses of 200 and 400 mg/kg were selected for pretreatment with DCW. The filament or intravascular occlusion method was used for middle cerebral artery occlusion (MCAO). The Triphenyl tetrazolium chloride (TTC) staining method was used to investigate the infarct zone and penumbra volume. The neuroprotective effect of DCW was measured by hematoxylin staining. Movement performance was evaluated from neurological deficit score, rotarod performance, and open field tests.
Results: TTC staining showed that the DCW/400 group could maintain the penumbra's structure and reduce the infarct volume compared to the Ctrl group (p<0.001). Histological studies confirmed the neuroprotective properties of DCW at doses of 200 and 400 mg/kg compared to the Ctrl group (p<0.01 and p<0.0001, respectively). The results of behavioral tests showed an improvement in behavioral performance in pretreatment 400 mg/kg doses compare to Ctrl group (p<0.0001).
Conclusion: The study showed that pretreatment with DCW with its neuron protection potential reduces the infarct area and restores motor function after MCAO.
- Topical application of medicinal plant oils in pediatric-related
disorders: A comparative review article based on traditional Persian
medicine
Abstract: Objective: Researchers have considered medicinal oils to prevent and treat pediatric diseases. In the traditional Persian medicine (TPM) doctrine, anointment is widely used in order to avoid and treat diseases. This study aimed to evaluate and reconcile the uses of anointment in children in TPM and the new studies.
Materials and Methods: Accordingly, TPM documents were scrutinized for anointments and their applications in pediatric disorders. Moreover, new studies were reviewed in Google scholar, PubMed, Medline, Scopus, and Web of Science until June 2022.
Results: In the health preservation field, TPM scholars have recommended daily anointment with some oils like sweet almonds in the early months after birth to improve growth, strengthen the body, and prevent dry skin, and new studies have confirmed the effectiveness of some oils accordingly. In the treatment field, various oils are recommended, namely sweet almond oil for weight disorders, violet oil for insomnia, olive oil and chamomile oil for functional constipation, infantile colic and enuresis, and olive oil for diaper rash and atopic dermatitis and new studies have shown their effectiveness. Sweet almond, chamomile, violet, olive, and rose oils are among the most widely used oils in Persian medicine for children, which we have discussed in this study.
Conclusion: Due to the non-invasive nature of anointment and the observation of minimal adverse effects in studies, it can be given attention for maintaining pediatric health and treating their diseases.
- Protective effects of a mixture of multi-strain native Iranian probiotics
on lead acetate-induced toxicity in the kidney of male rats: An integrated
biochemical, molecular and histopathological study
Abstract: Objective: In this study, the protective effects of native Iranian probiotics (Lactobacillus rhamnosus, Lactobacillus casei and Lactobacillus holoticus) on lead acetate (PbAc)-induced toxicity in the kidney of male rats were investigated using biochemical, molecular and histopathological approaches.
Materials and Methods: Twenty-one male Wistar rats were divided into three groups (n=7/group), including controls, PbAc recipient (10 mg/kg) and PbAc recipient (10 mg/kg) + probiotic mixture (109 CFU). PbAc and probiotics were gavage in the groups. On the 31st day, blood samples were used to measure serum concentrations of creatinine (Cr), blood urea nitrogen (BUN), sodium, total protein and potassium. Rats were dissected and renal tissues apoptotic and inflammatory genes were evaluated.
Results: PbAc increased serum concentrations of Cr, sodium, and urea, and decreased total protein and potassium, while it enhanced interleukine-6 (IL-6) and tumor necrosis factor -α (TNF- α) gene expression in kidney tissue compared to the control group. Probiotic mixture decreased Cr, BUN, and malondialdehyde and increased activity of catalase and superoxide dismutase enzymes in kidney tissue.
Conclusion: The results of the study showed that the native Iranian probiotics mixture can be used to protect the function and structure of the kidneys against toxic and oxidative damage induced by PbAc.
- Virtual screening of natural products as potential inhibitors of
SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp) and Spike
Protein: Database design, molecular docking and molecular dynamic study
Abstract: Objective: COVID-19 is caused by the SARS-CoV-2 virus. In this study, around 300 herbal compounds were screened virtually to find the best anti-COVID-19 structures.
Materials and Methods: An extensive search in electronic databases was done. Around 300 herbal compounds, which were previously proven to be antiviral structures, were extracted from articles and considered our primary database. Then, molecular docking studies were performed to find the best inhibitors of the main SARS-COV-2 proteins, including spike protein (PDB 7BWJ), RNA-dependent RNA polymerase (PDB 6M71) and main protease (PDB 5R7Z).
Results: The molecular docking and dynamics studies revealed that fangchinoline as an alkaloid could bind to the main protease of the virus more potent than lopinavir (-42.26 vs. -30.9 kJ/mol). Fangchinoline can be orally active based on drug-like properties. According to the molecular dynamic study, the complex between the fangchinoline and SARS-CoV-2 main protease is stable. chebulagic acid is a benzopyrene tannin that could inhibit RNA-dependent RNA polymerase (RdRp) better than remdesivir (-43.9 vs. -28.8 kJ/mol). The molecular dynamic study showed that chebulagic acid-RdRp interaction is stable and strong. Furthermore, suramin could neutralize different variants of COVID-19 spike proteins (wild type, and alpha and beta variants). However, suramin is not orally active but it is a potential inhibitor for different coronavirus spike proteins.
Conclusion: According to the promising in silico results of this study, fangchinoline, chebulagic acid and suramin could be introduced as potential lead compounds for COVID-19 treatment. We are hopeful to find a reliable remedy shortly through natural compounds.
- The preventive effects of Zataria multiflora and carvacrol and their
co-administration with pioglitazolne on systemic inflammation and
oxidative stress induced by paraquat inhalation in rats
Abstract: Objective: The present study aimed to assess the impact of the aqueous-ethanolic extract of Zataria multiflora (ZM), carvacrol (Car), and their co-administration with a PPAR activator, pioglitazone (Pio), on oxidative stress and inflammation induced by paraquat (PQ) inhalation at a systemic level.
Materials and Methods: The rats in the control group were exposed to saline and those of other groups to PQ (54 mg/m3) aerosols for 8 times on alternate days. Nine PQ groups were treated with saline, Car (20 and 80 mg/kg/day), ZM (200 and 800 mg/kg/day), Pio (5 mg/kg/day), dexamethasone (Dexa, 0.03 mg/kg/day), and low-dose ZM or Car + Pio for 16 days during the period of PQ exposure (n=6).
Results: Differential and total WBC counts, and malondialdehyde (MDA), interleukin (IL)-10, and tumor necrosis factor (TNF)-α levels were enhanced but catalase (CAT), thiol, and superoxide dismutase (SOD) levels were reduced in the blood in the PQ group (p<0.01 to p<0.001). All measured variables improved in groups treated with both doses of ZM, Car, Pio, ZM + Pio, Car+Pio, and Dexa vs the PQ group (p<0.05 to p<0.001). Most variables were more improved in combined treatment groups in comparison with three agents alone. The combination of ZM or Car, and Pio showed an impact on PQ inhalation-induced systemic changes.
Conclusion: The synergistic effect between Pio with ZM or Car indicates that these substances work together to enhance their individual effects.
- Comparison of effects of P-coumaric acid and coumarin on colorectal cancer
cell line by inducing apoptosis and autophagy
Abstract: Objective: Autophagy, as a cellular pathway involved in removing damaged proteins and organelles, performs a vital function in the homeostasis and fate of cells. Natural compounds of coumarin (CO) are found in a variety of herbs. Due to their many medicinal properties, including antitumor and anti-proliferative activity, they are involved in apoptosis and autophagy processes. This investigation desired to analyze the apoptotic and autophagic effects of p-coumaric acid (PCA) and CO on HT-29 cells cultured in fibrin hydrogel.
Materials and Methods: Cell viability and apoptotic and autophagic changes were evaluated by MTT assay, Acridine Orange, 4′,6-diamidino-2-phenylindole (DAPI), and monodansylcadaverine (MDC) staining. The expression Bax, Bad, Bcl2, Lc3, Beclin-1, P53 and Atg5 was respectively measured by qRT-PCR and Western blotting.
Results: CO (IC50=25 μM) and PCA (IC50=150 μM) had a dose- and time-dependent cytotoxic effect in HT-29 cells. So, the cytotoxic effects of CO were significantly higher than PCA and these differences were also evident in cell morphology investigations. The data illustrated a high expression of pro-apoptotic and pro-autophagic genes and a declined expression of anti-apoptotic and anti-autophagic genes.
Conclusion: CO (that was more potent) and p-coumaric acid-induced autophagy via PI3K/Akt/mTOR and AMPK/mTOR signaling on HT-29 cells.
- Evaluation of the effect of Foeniculum vulgare fruit and Echium amoenum
flower combination on the severity of physical and psychological symptoms
of premenstrual syndrome
Abstract: Objective: Echium amoenum (EA) and Foeniculum vulgare (FV) might be beneficial for the management of Premenstrual syndrome (PMS) due to their possible effects on sex hormones and neurotransmitters such as serotonin. This study aimed to investigate the effect of a combination of Echium and Fennel on the severity of physical and psychological symptoms of PMS.
Materials and Methods: This triple-blinded, randomized, controlled trial was conducted on 80 women. The subjects were assigned to two groups of intervention (receiving EA 2 g/day and FV 1 g/day, in the second two weeks of the cycle, in two consecutive cycles) and placebo control. The data collection tools included the PSST, DRSP, and SF36 questionnaires.
Results: Between-group differences in all subscales of DRSP were significant at one- and two-month time points (p<0.05). Bleeding volume was significantly increased in the intervention group, compared to the placebo group, two months after the intervention (p<0.05). Between-group comparison of the changes demonstrated significant differences in all subscales of SF36, except for limitations in usual role activities due to emotional problems (p=0.07).
Conclusion: Consumption of EA and FV combination improved the quality of life in women with PMS and exerted favorable changes in PMS symptoms.
- The cardioprotective properties of Persicaria maculosa and Citrus sinensis
extracts against doxorubicin-induced cardiotoxicity in mice
Abstract: Objective: This study assessed the cardioprotective properties of Persicaria maculosa (PME) and Citrus sinensis (CME) hydro-methanolic extracts, besides Citrus sinensis aqueous extract (CWE) against doxorubicin (DOX)-induced cardiotoxicity.
Materials and Methods: The extracts were characterized. Mice were divided into eight groups: control (saline), DOX, protected (injected with 200 mg/kg of PME, CWE or CME for 21 days, orally, and DOX), and extracts (PME, CWE or CME administration, orally, for 21 days). DOX was injected (5 mg/kg, ip) on days 8, 13 and 18 of the experiment. Cardiac tumor necrosis factor-alpha (TNF-α), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and carbonyl reductase 1 (CBR1) expression levels, besides superoxide dismutase, catalase, malondialdehyde, nitric oxide and total protein levels were evaluated. Serum lactate dehydrogenase, creatine phosphokinase cardiac isoenzyme, aspartate transaminase, cholesterol, triglycerides and creatinine levels, as well as the cardiac tissues were examined.
Results: Comparing with the control, DOX considerably (p<0.01) up-regulated TNF-α expression, malondialdehyde, nitric oxide, cardiac enzymes, lipids and creatinine levels, while it significantly (p<0.01) down-regulated Nrf2 and CBR1. Additionally, DOX interfered with antioxidant enzymes' activities (p<0.01). Conversely, protected groups showed a significant (p<0.01) amelioration of DOX-induced cardiotoxic effects.
Conclusion: The current study provides a new understanding of P. maculosa and C. sinensis cardioprotective mechanisms. The extracts' cardioprotective effects may be due to their antioxidant activities, ability to maintain the redox homeostasis through regulation of important antioxidant genes and primary antioxidant enzymes, and capability to recover inflammatory cytokines and lipids levels. Noteworthy, the tested extracts showed no toxic changes on the normal mice.
- Medicinal plants used in traditional medicine to enhance immunity: A
survey in the southeastern area of Morocco and a literature review
Abstract: Objective: The threat of immune escape and the discovery of antibiotic-resistant pathogens, as well as the failure of certain conventional drugs that are already in use for the symptomatic treatment of diseases, have prompted a re-evaluation of ancient therapeutic remedies such as phytotherapy, and aromatherapy. In this context, the present study aims to shed light on some medicinal plants mostly used by the population of the Daraa Tafilalet region to strengthen their immune systems, and to provide an up-to-date literature review on this subject.
Materials and Methods: A survey study was conducted using pre-prepared questionnaires addressed to the population of the Daraa Tafilalet region. MS Windows Excel and SPSS software were used for statistical analysis and results presentation. In addition, for the literature review, searches were conducted across several databases, including Google Scholar, Science Direct, Web of Science, PubMed, and Scopus, using medicinal plants, date products, enhance immunity, and essential oils as keywords.
Results: Among 142 participants interviewed, 108 used medicinal plants to improve their immune systems. However, 34 interviewers prefer conventional medicine. Date palm fruits and oregano were the most commonly used medicinal plants by the Daraa Tafilalet population to enhance the immune system, followed by anise, lavender, rosemary, thyme, and pennyroyal. These results are supported by literature data.
Conclusion: These results reflect the interesting traditional medical knowledge of this population, which merits being documented.
- Evaluating the efficacy of Terminalia chebula Retz. 5% cream compared to
hydroquinone 2% cream in the treatment of melasma
Abstract: Objective: Melasma is a multifactorial, chronic, acquired skin disorder of hyperpigmentation. Terminalia chebula Retz. (T. chebula) has shown antioxidant, anti-inflammatory and tyrosinase enzyme inhibitory activities. So, the present study was designed to evaluate the efficacy of T. chebula 5% cream compared to hydroquinone 2% cream in treating patients with melasma.
Materials and Methods: The formulation of T. chebula 5% cream was prepared. The stability and release study of the cream were performed. In this randomized, controlled, triple-blind clinical trial, participants with facial melasma were randomly assigned to receive T. chebula 5% cream or hydroquinone 2% cream at bedtime for 12 weeks. Modified Melasma Area and Severity Index (mMASI) scores were recorded for all the participants at the baseline and 4, 8, and 12 weeks after initiating the study.
Results: No statistically significant differences regarding mMASI scores were detected between T. chebula and hydroquinone groups at each time point. The reduction in mMASI scores was statistically significant (p<0.05) in T. chebula group 4, 8, and 12 weeks after initiating the study. However, it reached statistical significance (p<0.05) in hydroquinone group 8, and 12 weeks after the study initiation. The frequencies of side effects especially skin irritation were significantly (p<0.05) lower in T. chebula group.
Conclusion: T. chebula 5% cream could be as effective as hydroquinone 2% cream in treating melasma with fewer side effects.
- Roselle (Hibiscus sabdariffa L.) extract as an adjunct to valsartan in
patients with mild chronic kidney disease: A double-blind randomized
controlled clinical trial
Abstract: Objective: The objective of this study was to evaluate the effectiveness of Hibiscus sabdariffa L. extract (HS) as an adjunct to valsartan in the treatment of high blood pressure in patients with mild chronic kidney disease (CKD).
Materials and Methods: This trial was conducted in Gorgan, Iran. Seventy-two participants with CKD and high blood pressure were randomly assigned to either the HS group, receiving a 350 mg pill every 12 hr for 90 days along with 40 mg of valsartan every 12 hr, or the control group (40 mg valsartan + 12.5 mg hydrochlorothiazide). The primary objective was to assess the improvement of hypertension, while secondary objectives included the evaluation of proteinuria, albuminuria, kidney function, lipid profile, and electrolyte levels. Molecular docking analysis was performed to examine the mechanisms of action of the isolated components of HS.
Results: Out of 80 initial participants, 72 were included in the analysis. Both groups showed a significant reduction in blood pressure (p<0.001). The HS group demonstrated a statistically significant decrease in lipid profile (p<0.001). There were no statistically significant differences between the groups regarding the reduction of renal markers. Molecular docking analysis revealed that the compounds present in HS, particularly its anthocyanins and flavonoids, exhibited greater angiotensin-converting enzyme (ACE) inhibitory potential than hydrochlorothiazide in both domains. Moreover, the compounds met the criteria for drug likeness and Lipinski rules.
Conclusion: Adjunctive therapy with HS showed promising results in reducing hypertension and improving lipid profile in patients with CKD.
- Experimental and clinical studies on pharmacological actions of the genus
Achillea: A comprehensive and updated review
Abstract: Objective: Species of the genus Achillea (from the family Compositae or Asteraceae) are widely used for their numerous pharmacological properties. The present paper reviews pharmacological actions and their possible underlying molecular mechanisms reported for various species of Achillea.
Materials and Methods: Various databases including PubMed, Science Direct, and Scopus were used.
Results: Immunosuppressive, anti-inflammatory and anti-oxidant effects were shown for these plants. In addition, it was shown that these plants pose wound-healing properties and antimicrobial effects on various bacteria as well as antitumor effects on different cell lines. Achillea species showed anti-arrhythmic, anti-thrombotic, vasorelaxant, anti-hyperlipidemic, anti-hypertensive, hepatoprotective and gastroprotective effects. In addition, the plants showed different endocrine effects such as anti-diabetic, estrogenic and anti-spermatogenic properties. Neurological effects of the plants also included anti-nociceptive and anti-anxiety actions. Clinical studies also indicated therapeutic effect of A. millefolium on multiple sclerosis, chemotherapy-induced oral mucositis in cancer patients, and dysmenorrhea but did not affect atopic dermatitis.
Conclusion: Achillea species could be of therapeutic potential for treating of a wide range of diseases but further investigations are needed regarding the other properties of Achillea plants.
- Effect of Nigella sativa on dexamethasone-induced testicular toxicity in
mice
Abstract: Objective: The aim of the current study was to assess the effects of Nigella sativa essential oil on testicular toxicity in mice induced by dexamethasone.
Materials and Methods: Forty NMRI mice were randomly divided into four groups. The first group (Sham) received 1 ml per day of normal saline by intraperitoneal (i.p.) injection for 7 days. The second group (Control) received (i.p) injection of 5 mg/kg dexamethasone for 7 days. The third group (Dexa+ N.S 5 mg/kg) received dexamethasone (5 mg/kg) and gavaged 5 mg/kg N. sativa essential oil for 7 days. The fourth group (N.S 5 mg/kg) for 7 days was gavaged 5 mg/kg N. sativa. Histopathology of testis, spermatogenesis, and sperm fertility rate were assessed.
Results: The results of histopathology assessments showed that in the third group, all histopathology criteria were decreased compared to the second group. The number of seminiferous tubules that had abnormal spermatogenesis in Johnsen’s score was slightly decreased in the third group compared to the second group. Furthermore, in the third group, embryo formation criteria were increased.
Conclusion: The data of this research demonstrate that N. sativa improves spermatogenesis defects and sperm fertility in mice treated with dexamethasone.
- Aloe vera supplementation improves cardiovascular risk factors in
hemodialysis patients: A randomized, double-blind, placebo-controlled
trial
Abstract: Objective: This study assessed the effects of Aloe vera supplementation on serum inflammatory factors, blood sugar and lipid profiles in hemodialysis patients.
Materials and Methods: Totally, 50 hemodialysis patients were allocated randomly to either Aloe vera or placebo groups. The Aloe vera group received 2 Aloe vera capsules daily for 8 weeks (500 mg/day). Serum C-reactive protein (hs- CRP), Fasting blood glucose (FBS), and lipid profiles levels were evaluated at the baseline and the end of the eighth week.
Results: Aloe vera supplementation for 8 weeks was associated with a significant reduction of serum hs- CRP (p=0.004), total cholesterol (p=0.01), low density lipoprotein (LDL) (p=0.02) leves and increased high density lipoprotein (HDL) (p=0.002) concentration in the hemodialysis patients.
Conclusion: Aloe vera supplementation is beneficial in improvement of cardiovascular risk factors in hemodialysis patients.
- Apigenin attenuates serum concentrations of TNF-a, interleukin 1b and
interleukin 6 in lipopolysaccharide-stimulated rats
Abstract: Objective: The use of flavonoids is increasing due to their cost-effectiveness and less adverse reaction. Therefore, the effect of apigenin on lipopolysaccharide (LPS)-induced inflammation was investigated by measuring IL-1b, IL-6, and TNF-a, of serum in the male rats.
Materials and Methods: Ninety male wistar rats were divided in 6 groups included; control, sham, dexamethasone 15 mg/kg, intraperitoneally (i.p.), and apigenin (5, 15, and 30 mg/kg, i.p). Thirty minutes after the administration of solvent or apigenin, LPS (30 μg/kg, i.p) was injected. At time intervals of 4, 12 and 24 hr after injection, blood samples were taken and the concentrations of TNF-a, IL-1b and IL-6 were measured by enzyme-linked immunosorbent assay.
Results: Compared to the control, apigenin (5 mg/kg) decreased the level of TNF-a, and IL-1b in a period of 24 hr (p<0.05). The concentration of IL-6 decreased significantly by apigenin (15 mg/kg) 24 hr after injection (p<0.05). Apigenin (30 mg/kg) decreased the level of TNF-a, at all three time points (4 hr; p<0.05, 12 hr; p<0.01, and 24 hr; p<0.01), and the level of IL-1b (p<0.01), 24 hr and the level of IL-6 at 4 hr (p<0.05), and 24 hr (p<0.01) after LPS injection.
Conclusion: Apigenin can suppress serum inflammatory cytokines, similar to dexamethasone.
- An in vitro antiviral evaluation of punicalagin toward influenza A virus
Abstract: Objective: Influenza complications are mild to serious, and can cause death in some cases. A great deal of attention has been paid in recent years to the development and use of new antiviral compounds to overcome drug resistance in certain strains of the influenza virus and treat the clinical implications. This study aimed to investigate the antiviral effect of punicalagin and its associated mechanism against influenza A (H1N1) virus in vitro.
Materials and Methods: the ant-influenza activity of punicalagin was studied in Madin-Darby Canine Kidney (MDCK) cells using influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) using Hemagglutinin assay (HA) and 50% tissue culture infective dose (TCID50). Then, the inhibition of haemagglutination, virucidal activity, inhibitory effect at different times, replication of viral RNA and expression of viral genes were investigated.
Results: Punicalagin could inhibit influenza virus infection with 50% inhibitory concentration (IC50) of 3.98 μg/ml and selectivity index (SI) value of 6.1. Punicalagin decreased virus titers with an inhibitory effect on virus hemagglutination (p<0.05). Punicalagin also inhibited viral adsorption. The results of virus RNA replication and viral mRNA (NS1 and HA) expression after treatment with punicalagin showed significant suppression of viral mRNA expression but no effect on replication of viral RNA.
Conclusion: The results of the present study indicated that punicalagin was effective against influenza infection most probably via inhibition of haemagglutination activity and virus binding.
- Herbal and nano-based herbal medicine: New insights into their therapeutic
aspects against periodontitis
Abstract: Objective: Periodontitis is a type of prevalent chronic inflammatory disorder resulting in a failure in the function of tissues supporting the tooth, like gingiva, alveolar bone, and periodontal ligament. Although antibiotic therapy is a common therapy for periodontitis cases, this approach can cause some adverse effects in these patients. Thus, finding an effective curative option with low side effects is still a puzzle.
Materials and Methods: This narrative review was conducted on the effects of herbal and nano-based herbal medicine against periodontitis by searching different databases such as Google Scholar, PubMed, Scopus, Web of Science, Science Direct, and Scientific Information Databases.
Results: According to published studies, some popular herbal formulations, such as Aloe vera, curcumin, Melaleuca alternifolia, and Scutellaria baicalensis Georgi, can be effective in periodontitis treatment. However, these herbal products may be accompanied by some pharmacological limitations, such as poor bioavailability, instability, and weak water solubility. On the other hand, harnessing nano-based herbal formulations can elevate the bioavailability, diminish toxicity, and omit repeated administration of drugs.
Conclusion: Herbal and nano-based herbal products can create a good chance to treat periodontitis efficiently.
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