Protective effects of Panax ginseng as a medical food against chemical toxic agents: molecular and cellular mechanisms.

Humans are exposed to different types of toxic agents, which may directly induce organ malfunction or indirectly alter gene expression, leading to carcinogenic and teratogenic effects, and eventually death. Ginseng (Panax ginseng) is the most valuable of all medicinal herbs. Nevertheless, specific data on the antidotal mechanisms of this golden herb are currently unavailable. Based on the findings of in vitro, in vivo, and clinical studies, this review focused on the probable protective mechanisms of ginseng and its major components, such as protopanaxadiols, protopanaxatriols, and pentacyclic ginsenosides against various chemical toxic agents. Relevant articles from 2000 to 2023 were gathered from PubMed/Medline, Scopus, and Google Scholar. This literature review shows that P. ginseng and its main components have protective and antidotal effects against the deteriorative effects of pesticides, pharmaceutical agents, including acetaminophen, doxorubicin, isoproterenol, cyclosporine A, tacrolimus, and gentamicin, ethanol, and some chemical agents. These improvements occur through multi-functional mechanisms. They exhibit antioxidant activity, induce anti-inflammatory action, and block intrinsic and extrinsic apoptotic pathways. However, relevant clinical trials are necessary to validate the mentioned effects and translate the knowledge from basic science to human benefit, fulfilling the fundamental goal of all toxicologists.

Evaluation of the Effect of Pistacia atlantica Oleoresin on Blood Sugar, Pressure and Lipids in Patients With Type 2 Diabetes: A Single-Blind, Placebo-Controlled Trial.

BACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disorder characterised by high blood sugar (BS) levels due to impaired insulin production or insulin resistance. It is a global health concern with significant implications for morbidity and mortality. Persian medicine has long utilised natural remedies, such as Pistacia atlantica Desf., for various diseases. In this randomised clinical trial, the effects of P. atlantica oleoresin in the improvement of lipid profiles, glucose indices and blood pressure (BP) were assessed in patients with Type 2 DM. MATERIALS AND METHODS: In this randomised, single-blind, placebo-controlled study, 42 patients with Type 2 DM were randomly allocated to receive either P. atlantica oleoresin or placebo capsule for 3 months. Patients were evaluated prior to and 12 weeks after the beginning of the intervention, in terms of changes in lipid profiles, glucose indices and BP. RESULTS: After 3 months, the mean BP in patients with DM receiving P. atlantica oleoresin was significantly reduced compared with the baseline (p = 0.001). Also, these changes were significantly higher than those of the control group. The mean of total cholesterol (p = 0.89), low-density lipoprotein (LDL) (p = 0.43) and triglyceride (TG) (p = 0.98) in the intervention group after 3 months was lower than that in the control group, but this difference was not statistically significant. CONCLUSION: After 3 months, there was no significant difference between the P. atlantica and control groups in terms of blood sugar and lipid profiles. The mean BP in patients with DM receiving P. atlantica oleoresin was significantly reduced compared with that in the beginning of the study. Also, these changes were significant compared with the control group.

Effects of Pistacia genus on gastrointestinal tract disorders: A systematic and comprehensive review.

Gastrointestinal (GI) disorders characterized by persistent and recurrence gastrointestinal symptoms are prevalent. The genus Pistacia is widely emphasized as the relief of gastrointestinal diseases in traditional medicine. This review aimed to investigate the latest evidence on the effect of the Pistacia genus on GI tract disorders. The systematic search was performed following to PRISMA guidelines. The databases PubMed and Scopus were searched from 1980 to 2022 with restrictions to the original studies. Electronic databases were searched in title/abstract, using the keywords relevant to GI tract disorders. Forty-eight studies were included in this review following the inclusion criteria. Fifteen and 22 studies were clinical and animal studies, respectively, of which 6 clinical and 13 animal studies were on Inflammatory Bowel diseases. Seven clinical studies were on functional GI disorders. The most pieces of evidence from animal and clinical studies were on the intestinal inflammation and peptic ulcer affecting the inflammation as well as oxidative stress through different mechanistic pathways. The most referred active phytochemicals seem to be terpenoid compounds. Various in vitro studies have also shown the inhibitory activity of the different plant parts of Pistacia herbs on several GI tract cancer cells. Available scientific evidence supports the effects of various components of Pistacia genus plants in the field of GI tract diseases, especially digestive inflammations. Further studies are required to systematically evaluate the natural products of the genus Pistacia, particularly in the context of digestive disorders.

Evaluation of the cytotoxic activities of the essential oil from Pistacia atlantica Desf. oleoresin on human gastric cancer cell lines.

Numerous herbal products have been the subject of research regarding their potential role in cancer prevention or adjuvant therapy. Pistacia atlantica and its main phytochemicals have garnered significant attention for their potential anti-cancer effects. The study aimed to assess the growth inhibitory effects of P. atlantica essential oil (PAEO) on MKN-45 and AGS cells. This study quantified the volatile compounds in PAEO using Gas Chromatography-Mass Spectrometry (GC-MS). Subsequently, MKN-45 and AGS cells were treated with varying concentrations of PAEO (5%, 2.5%, 1.25%, 0.625%, 0.3125%, 0.156%, 0.0781%, 0.0391%, 0.0195%) for 24 h. Cell viability was evaluated through the MTT assay. The impact of PAEO on gene expression was investigated by quantifying the mRNA levels of Bax and Bcl2 in the various experimental groups using quantitative Real-Time PCR (qRT-PCR) analysis. Additionally, flow cytometry was utilized to evaluate apoptosis in the treated cells. The analysis of PAEO revealed that α-pinene was the predominant monoterpene, constituting 87.9% of the oil composition. The cytotoxic effects of PAEO were evaluated, and it was found that the oil significantly reduced the viability of MKN-45 and AGS cells. The IC50 for MKN-45 cells was determined to be 1.94 × 10-3% after 24 h of treatment, while for AGS cells the IC50 was 2.8 × 10-3% after 24 h. Additionally, the research revealed that PAEO triggered a notable rise in apoptotic cells in both AGS and MKN-45 cell lines. Moreover, at the molecular level, the findings indicated an increase in Bax expression and a decrease in Bcl2 mRNA expression, providing further evidence of the induction of apoptosis in both MKN-45 and AGS cell lines following PAEO treatment. The findings of this study offer evidence supporting the cytotoxic effects of PAEO on gastric cancer cell lines by promoting apoptosis. The findings suggest that PAEO may offer potential as a therapeutic candidate in managing and treating gastric cancer.

Randomized controlled trial of the effectiveness of olive and black seed oil combination on pain intensity and episiotomy wound healing in primiparous women: A study protocol.

BACKGROUND: Episiotomy is associated with side effects, such as pain and wound infection. Additionally, discomfort after episiotomy affects the quality of life of both the mother and the baby. Medicinal herbs are one alternative method for the treatment of episiotomy wounds. This study will investigate the effectiveness of the combination of olive and black seed oil on pain intensity and the healing of episiotomy wounds in primiparous women. METHODS: This randomized clinical trial will be conducted on primiparous women who have had a normal delivery with an episiotomy. There are 3 groups in this study: one group will receive a combination of olive oil and black seed oil, another group will receive olive oil alone, and the use of oils will start 24 hours after delivery. Ten drops will be applied topically 3 times a day for 10 days. The third group (control) will receive only routine care. Data will be collected through a demographic characteristics questionnaire, REEDA (Redness, Edema, Ecchymosis, Discharge, and Approximation) Scale, and Visual Analog Scale. To determine and compare the effects of pharmaceutical interventions on pain intensity and episiotomy wound healing in the groups, an analysis of variance (ANOVA) test with repeated measurements will be used with SPSS version 22. DISCUSSION: The results of this study will show the effects of a combination of olive and black seed oil, as well as olive oil alone, on pain intensity and episiotomy wound healing in primiparous women. The positive effects observed in this trial with these oils could be valuable for women who have undergone an episiotomy.

Effect of Medicago sativa seed powder (Plus vitamin E vs. vitamin E alone) on semen analysis in men with idiopathic infertility: A double blind randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Different parts of the alfalfa plant (Medicago sativa L.), especially its seeds, have been introduced as a semen quality enhancer in the folk medicine of different regions of Iran as well as in the traditional Persian medicine (PM) books. The seeds of this plant are also used in many combined medicines to treat male infertility in PM. AIM OF THE STUDY: This study was designed to investigate the effect of M. sativa seed powder plus vitamin E vs. vitamin E alone on semen analysis of men with idiopathic infertility. MATERIALS AND METHODS: In this randomized clinical trial, 60 participants were randomly divided into two groups and then received M. sativa seed powder (6 g daily) or placebo for three months, as add-on to vitamin E (100 U). Results of semen analysis (sperm total count, motility, and morphology as well as semen volume) of these two groups and their changes were compared before and after treatment as the primary outcome. The number of pregnancies after one month and probable side effects were also assessed. RESULTS: After 12 weeks, sperm total count changed from 36.2 ± 21.8 × 106/ml to 48.5 ± 19.1 × 106/ml in M. sativa and from 39.5 ± 23.5 × 106/ml to 41.2 ± 20.9 × 106/ml in placebo, percentage of normal morphology changed from 1.8 ± 0.8% to 2.6 ± 1.2 % in M. sativa and from 2.0 ± 0.9% to 2.6 ± 1.2% in placebo and percentage of motile sperm changed from 36.5 ± 11.8 % to 39.7 ± 12.0% in M. sativa and from 39.3 ± 10.1 % to 38.1 ± 12.1% in placebo. The improvements in M. sativa group are significantly better than placebo group (P = 0.00, 0.01 and 0.04, respectively). However, semen volume decreased in both groups, but its changes were not significant. The number of pregnancies was four in the intervention and zero in placebo group. One case with abdominal bloating and one with respiratory allergy withdrew from the intervention group. No other adverse effect was reported. CONCLUSIONS: In this study, significant improvement was detected in sperm parameters (except semen volume) of men with idiopathic infertility in M. sativa plus vitamin E group in compare to vitamin E alone after 12 weeks. These findings suggest that the M. sativa, as a complementary therapy, may have a beneficial effect on semen quality. More clinical trials with larger sample size are needed.

The effect of oral use of concentrated pomegranate juice by mothers on hyperbilirubinemia in neonates under phototherapy: A randomized clinical trial.

Background: Hyperbilirubinemia is a common problem in neonates that causes hospitalization. The aim of this study was to investigate the effects of concentrated pomegranate juice (CPJ) consumption by breastfeeding mothers on neonatal hyperbilirubinemia. Materials and Methods: In this open-labeled, add-on, randomized clinical trial, 86 breastfeeding mothers and their neonates were allocated into two groups. In the control group, neonates received phototherapy. Besides neonates' phototherapy in the intervention group, their mothers received CPJ (1 tablespoon [15 g] three times a day) up to discharge. The bilirubin level was the primary outcome. The duration of phototherapy, the duration of hospital stay, and the need for exchange transfusions were secondary outcomes. Results: CPJ reduced the bilirubin level of hospitalized neonates within 48 h after consumption (P = 0.048, standard mean difference = 0.648). It also resulted in reduced duration of hospital stay and faster discharge of the neonates. Furthermore, in 48 h after discharge, bilirubin was significantly lower in the CPJ group (P = 0.003, partial eta squared = 0.123). Conclusion: Compared to the control group, consumption of CPJ by lactating mothers whose infants underwent phototherapy resulted in lower bilirubin levels, shorter hospital stay, and faster discharge.

Effect of Cassia fistula L. aqueous extract in maternal reproductive outcome, some serum indices and fetal anomaly frequency in rat.

Background: Cassia fistula was used traditionally as laxative in pregnant women. Nevertheless, its fetal and maternal effects in pregnancy have not been studied yet. Methods: Oral (Lethal Dose, 50%) LD50 was determined in mice. In addition, a control group, pregnant rats in other 5 experimental groups (n=12) received orally C. fistula aqueous extract (500, 1000 and 2000 mg/kg), tween80 (10%) and distilled water during pregnancy up to the delivery (21-23 days). Some serum indices were evaluated in maternal blood samples after delivery. Histopathologic and histomorphometric evaluations were performed on the selected slices of newborn rats. Results: Anthraquinone content of the aqueous extract was 0.34% w/w. Oral LD50 was obtained more than 5000mg/kg. No abortions and newborn anomalies were observed in groups. The height and weight of the offspring were significantly reduced by the administration of 500, and 2000 mg/kg of extract compared to control. There was no significant change in maternal blood urea and creatinine. Higher concentration (2000mg/kg) led to ALT elevation. ALS levels decreased dose-dependency in treatment groups comparing to control. Histopathological findings showed significant lung vascular congestion, and hypertrophy of heart in group tween80, and significant hepatic parenchymal inflammation in tween80 and 2000mg/kg and 1000mg/kg groups. In all tissues of all groups, malpighian body area and bowman's capsule space significantly increased compared to the control group. Conclusion: It seems C. fistula extract is safe in pregnancy. Because of confounding role of tween80 in histopathological finding, more research is necessary.

The effect of Cassia fistula L. syrup in geriatrics constipation in comparison with the lactulose: A randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Cassia fistula is widely used in traditional Persian Medicine as a mild laxative. The rate of chronic constipation increases above the age of 60. AIM OF THE STUDY: This study aimed to investigate the effect of Cassia fistula syrup (CFS) on geriatric constipation. MATERIALS AND METHODS: This clinical trial study was performed on 70 aged patients who were referred to the clinic of gastroenterology of Rouhani Hospital, Babol, North of Iran. Patients were randomly divided into two groups of CFS or Lactulose with a dose of 30 ccs/day. Patients were visited two weeks after entering the study to evaluate the frequency of defecation, feeling of incomplete emptying after defecation, manual maneuver, consistency of stool, and also the quality of life. RESULTS: The frequency of defecation per week varied from 1.82 ± 1.16 to 8.36 ± 3.44 in the CFS group after 2 weeks of intervention that was significantly more than the Lactulose that changed from 2.16 ± 1.46 to 5.66 ± 2.96 (P-value = 0.023, partial eta square = 0.079, NNT = 4). The quality of life, the percent of straining, lumpy or hard stool, pain during defecation, and the consistency of stool based on VAS were significantly better in the CFS group. The sensation of incomplete defecation, anorectal obstruction, and manual maneuvering were not different significantly between groups. CONCLUSION: CFS can be more effective than Lactulose on geriatric constipation.

Quantification of Flavonoids in Alpinia officinarum Hance. via HPLC and Evaluation of its Cytotoxicity on Human Prostate Carcinoma (LNCaP) and Breast Carcinoma (MCF-7) Cells.

BACKGROUND: Various plant species have been shown to be effective in the prevention or adjuvant therapy of cancer. Alpinia officinarum and its main phytochemicals have also been the subject of several studies for their anticancer properties. OBJECTIVE: The objective of this study is to analyze the extracts of A. officinarum to quantify flavonoids and to evaluate the growth inhibitory effects of the extracts on MCF-7 and LNCaP cells. METHODS: A. officinarum aqueous and hydroalcoholic extracts were analyzed by using High-Performance Liquid Chromatography (HPLC) for the quantification of three flavonoid compounds. Then, MCF-7, LNCaP, and fibroblast cells were treated with several concentrations (25, 50, 100, 200, and 400 µg/mL) of extracts (24, 48 and 72h). Cell viability was assessed using an MTT assay. Flow cytometry was conducted to evaluate apoptosis. RESULTS: Galangin and kaempferol (3.85 and 1.57 mg/g dry extract) were quantified, respectively, in hydroalcoholic and aqueous extracts using a validated method. The hydroalcoholic extract significantly decreased the viability of MCF-7 (IC50: 43.45µg/mL for 48h) and LNCaP cells (IC50: 168 µg/mL for 48h). The aqueous extract reduced cancer cell viability by more than 50% only at 200 and 400 µg/mL (72 h). Treatment of primary fibroblasts with both extracts showed no significant decrease in cell viability (25-100 µg/mL; 24 and 48h). The hydroalcoholic extract induced a significant increase in apoptotic cells in both MCF-7 and LNCaP cells. CONCLUSION: Obtained results demonstrated the cytotoxicity of A. officinarum through apoptosis induction in two cancer cell lines. Further investigations are required to determine the underlying apoptotic cell death mechanisms induced by A. officinarum in cancerous cells.

Natural products against cisplatin-induced male reproductive toxicity: A comprehensive review.

Cisplatin is widely used as one of the most effective anticancer agents in the treatment of some neoplasms. Reproductive toxicity is the most common outcome associated with cisplatin testicular damage. Alternative natural medicines for treating male testicular disorders and infertility have received extensive attention in research. Natural products, medicinal herbs, and their secondary metabolites have been shown as promising agents in the management of testicular damage induced by chemotherapy drugs. This study aimed to review the research related to natural substances that are promising in mitigation of the cisplatin-induced toxicity in the reproductive system. PubMed and Scopus were searched for studies on various natural products for their potential protective property against reproductive toxicity induced by cisplatin from 2000 to 2020. Eligibility was checked based on selection criteria. Fifty-nine articles were included in this review. Mainly in animal studies, several natural agents have positively affected cisplatin-reproductive-toxicity factors, including reactive oxygen species, inflammatory mediators, DNA damage, and activation of the mitochondrial apoptotic pathway. Most of the natural agents were investigated in short-term duration and high doses of cisplatin exposure, considering their antioxidant activity against oxidative stress. Considering antioxidant properties, various natural products might be effective for the management of cisplatin reproductive toxicity. However, long-term recovery of spermatogenesis and management of low-dose-cisplatin toxicity should be considered as well as the bioavailability of these agents before and after treatment with cisplatin without affecting its anticancer activity.

Chemoprotective and chemosensitizing effects of apigenin on cancer therapy.

BACKGROUND: Therapeutic resistance to radiation and chemotherapy is one of the major obstacles in cancer treatment. Although synthetic radiosensitizers are pragmatic solution to enhance tumor sensitivity, they pose concerns of toxicity and non-specificity. In the last decades, scientists scrutinized novel plant-derived radiosensitizers and chemosensitizers, such as flavones, owing to their substantial physiological effects like low toxicity and non-mutagenic properties on the human cells. The combination therapy with apigenin is potential candidate in cancer therapeutics. This review explicates the combinatorial strategies involving apigenin to overcome drug resistance and boost the anti-cancer properties. METHODS: We selected full-text English papers on international databases like PubMed, Web of Science, Google Scholar, Scopus, and ScienceDirect from 1972 up to 2020. The keywords included in the search were: Apigenin, Chemoprotective, Chemosensitizing, Side Effects, and Molecular Mechanisms. RESULTS: In this review, we focused on combination therapy, particularly with apigenin augmenting the anti-cancer effects of chemo drugs on tumor cells, reduce their side effects, subdue drug resistance, and protect healthy cells. The reviewed research data implies that these co-therapies exhibited a synergistic effect on various cancer cells, where apigenin sensitized the chemo drug through different pathways including a significant reduction in overexpressed genes, AKT phosphorylation, NFκB, inhibition of Nrf2, overexpression of caspases, up-regulation of p53 and MAPK, compared to the monotherapies. Meanwhile, contrary to the chemo drugs alone, combined treatments significantly induced apoptosis in the treated cells. CONCLUSION: Briefly, our analysis proposed that the combination therapies with apigenin could suppress the unwanted toxicity of chemotherapeutic agents. It is believed that these expedient results may pave the path for the development of drugs with a high therapeutic index. Nevertheless, human clinical trials are a prerequisite to consider the potential use of apigenin in the prevention and treatment of various cancers. Conclusively, the clinical trials to comprehend the role of apigenin as a chemoprotective agent are still in infancy.

A Comparison of the Effect of Topical Preparation of Sambucus ebulus L. and Hydrocortisone on Hand Eczema: A Double-Blind Randomized Controlled Trial.

Objectives: Corticosteroids as the main treatment of hand eczema can cause major side effects. This study compared the effect of topical preparation of Sambucus ebulus L. leaves and hydrocortisone on the severity of hand eczema. Design: Ninety-four patients with hand eczema aging 18-60 years were recruited in two groups (S. ebulus vs. hydrocortisone). Interventions: The patients used topical medications twice a day and were followed for 4 weeks. The observations were made at the first visit, and also second and fourth weeks of the study. Outcome measures: The primary outcomes were changes in the severity of hand eczema (hand eczema severity index [HECSI]) and life quality (dermatology life quality index [DLQI]). Secondary outcomes were the rate of healing and the severity of itching. Results: Thirty-eight patients in hydrocortisone and 43 in S. ebulus fulfilled all phases of the follow-up. In both groups, the HECSI, itching scores decreased over time without any significant difference between the groups (p = 0.49, 0.57, respectively). The DLQI scores were significantly better in the S. ebulus group (p = 0.02) after 4 weeks of medication. There was no significant difference between the healing rates of the two groups (p = 0.33). Conclusions: Topical use of S. ebulus can be as effective as that of hydrocortisone when it comes to reducing the severity of hand eczema.

Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review.

Although the rates of many cancers are controlled in Western countries, those of some cancers, such as lung, breast, and colorectal cancer are currently increasing in many low- and middle-income countries due to increases in risk factors caused by development and societal problems. Additionally, endogenous factors, such as inherited mutations, steroid hormones, insulin, and insulin-like growth factor systems, inflammation, oxidative stress, and exogenous factors (including tobacco, alcohol, infectious agents, and radiation), are believed to compromise cell functions and lead to carcinogenesis. Chemotherapy, surgery, radiation therapy, hormone therapy, and targeted therapies are some examples of the approaches used for cancer treatment. However, various short- and long-term side effects can also considerably impact patient prognosis based on clinical factors associated with treatments. Recently, increasing numbers of studies have been conducted to identify novel therapeutic agents from natural products, among which plant-derived bioactive compounds have been increasingly studied. Naringin (NG) and its aglycone naringenin (NGE) are abundantly present in citrus fruits, such as grapefruits and oranges. Their anti-carcinogenic activities have been shown to be exerted through several cell signal transduction pathways. Recently, different pharmacological strategies based on combination therapy, involving NG and NGE with the current anti-cancer agents have shown prodigious synergistic effects when compared to monotherapy. Besides, NG and NGE have been reported to overcome multidrug resistance, resulting from different defensive mechanisms in cancer, which is one of the major obstacles of clinical treatment. Thus, we comprehensively reviewed the inhibitory effects of NG and NGE on several types of cancers through different signal transduction pathways, the roles on sensitizing with the current anticancer medicines, and the efficacy of the cancer combination therapy.

The effect of Achillea Millefolium L. on vulvovaginal candidiasis compared with clotrimazole: A randomized controlled trial.

INTRODUCTION: Vulvovaginal candidiasis is the second most common cause of vulvovaginal infections. The aim of this study is to evaluate the effectiveness of vaginal cream of Achillea millefolium extract in women with vulvovaginal candidiasis in comparison with vaginal clotrimazole. MATERIALS AND METHODS: This double-blind randomized clinical trial study was conducted on 80 women diagnosed with vulvovaginal candidiasis clinically and by laboratory test; 40 women received vaginal cream clotrimazole 1 % and 40 received vaginal cream containing the aqueous extract of A. millefolium for 7 days. Clinical and laboratory assessments were performed before and after the intervention. Minimum inhibitory concentration of the extract was evaluated with Broth micro-dilution procedure. RESULTS: The Dermatology life quality index score showed significant reduction in both groups after treatment, but it was significantly more reduced in control group (p < 0.05). Improvement in vulvar erythema was observed in both groups with no statistically difference (p = 0.1). Vaginal culture was negative in term of Candida in 28(77 %) patients of control group and in 18(53 %) patient of experimental group (p < 0.05). The Minimum inhibitory concentration of the extract was 37.5 mg/mL for the standard strain. DISCUSSION AND CONCLUSION: Study results showed that vaginal cream containing A. millefolium could reduce the complaints of vulvovaginal candidiasis. But, future studies with a larger sample size and different dosages are recommended to assess the outcomes of this new treatment.

Evaluation of the effect of Silybum marianum extract on menopausal symptoms: A randomized, double-blind placebo-controlled trial.

The tendency to use herbs to manage menopausal symptoms has increased in recent years. The purpose of this study was to evaluate the effect of Silybum marianum (L.) compared with placebo in women with hot flashes. Eighty women were randomly allocated into two equal groups (S. marianum extract [400 mg/d] or placebo capsules). Hot flashes frequency and severity were evaluated in 12 weeks with the Greene Climacteric Scale (GCS) and the Hot Flash Related Daily Interference Scale (HFRDIS). The data were analyzed in SPSS software using t-test, Mann-Whitney, chi-square test and repeated measure analysis. Hot flashes frequency and severity decreased from 4.32 ± 0.20/day to 1.31 ± 0.15/day and from 5.25 ± 0.22 to 1.62 ± 0.08, respectively, during the study in test group (p < .001) which were significantly better than effects of placebo in all steps of study (p < .001). Significant decreases in GCS and HFRDIS scores were also detected in S. marianum group compared with placebo after 4, 8 and 12 weeks (p < .001). The results showed that S. marianum can decrease frequency and severity of hot flashes significantly. Considering the safety and high consumption of this herbal medicine worldwide, its use in women with menopausal symptoms can be helpful.

Targeting Ubiquitin-Proteasome Pathway by Natural Products: Novel Therapeutic Strategy for Treatment of Neurodegenerative Diseases.

Misfolded proteins are the main common feature of neurodegenerative diseases, thereby, normal proteostasis is an important mechanism to regulate the neural survival and the central nervous system functionality. The ubiquitin-proteasome system (UPS) is a non-lysosomal proteolytic pathway involved in numerous normal functions of the nervous system, modulation of neurotransmitter release, synaptic plasticity, and recycling of membrane receptors or degradation of damaged and regulatory intracellular proteins. Aberrant accumulation of intracellular ubiquitin-positive inclusions has been implicated to a variety of neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), Amyotrophic Lateral Sclerosis (ALS), and Multiple Myeloma (MM). Genetic mutation in deubiquitinating enzyme could disrupt UPS and results in destructive effects on neuron survival. To date, various agents were characterized with proteasome-inhibitory potential. Proteins of the ubiquitin-proteasome system, and in particular, E3 ubiquitin ligases, may be promising molecular targets for neurodegenerative drug discovery. Phytochemicals, specifically polyphenols (PPs), were reported to act as proteasome-inhibitors or may modulate the proteasome activity. PPs modify the UPS by means of accumulation of ubiquitinated proteins, suppression of neuronal apoptosis, reduction of neurotoxicity, and improvement of synaptic plasticity and transmission. This is the first comprehensive review on the effect of PPs on UPS. Here, we review the recent findings describing various aspects of UPS dysregulation in neurodegenerative disorders. This review attempts to summarize the latest reports on the neuroprotective properties involved in the proper functioning of natural polyphenolic compounds with implication for targeting ubiquitin-proteasome pathway in the neurodegenerative diseases. We highlight the evidence suggesting that polyphenolic compounds have a dose and disorder dependent effects in improving neurological dysfunctions, and so their mechanism of action could stimulate the UPS, induce the protein degradation or inhibit UPS and reduce protein degradation. Future studies should focus on molecular mechanisms by which PPs can interfere this complex regulatory system at specific stages of the disease development and progression.

Nine Steps to Discover New Medicines from Traditional Sources: The Example of Persian Medicine.

Objectives: Developing a new medicine is a costly and time-consuming process. This study presents a novel method to collate a new materia medica from previously documented traditional Persian medicine (TPM) references. A well-documented materia medica will facilitate a quick and easy process to find traditional medicine for specific symptoms or diseases. Materials and methods: A nine-step algorithm is proposed to collate a new materia medica by searching and matching descriptions and references stated in various traditional Persian literature: (1) finding the equivalent of traditional description of symptoms or diseases; (2) determining the keywords to search in the references of TPM, including The Canon of Medicine (Book by Avicenna); (3) determining the best references of TPM for the aim of the study; (4) weighing up the references (a) based on the prominence of the author's prominence (b) determining whether the references are the author's own clinical findings or has citation from other scholars been used, (c) the popularity of the book that the references feature in, among other later scholars of TPM, the geographical and historical span across which the book has been distributed; (5) searching the references using keywords of symptoms or diseases; (6) finding the synonyms of terminologies in the various materia medicas and categorizing the findings; (7) revision (of references found) to ensure that nothing is neglected; (8) scoring the findings based on the defined criteria; (9) prioritization: sorting the materia medica based on the total scores. Some important economic, cultural or historical factors cannot be included in the main process of prioritization during the initial searching of the TPM materia medica. Therefore, it is necessary to take these factors into account after discovering the medicine and before using in practice to ascertain that they are a good match of a specific treatment, disease or symptom. Conclusion: A process to compile a new materia medica has been proposed which will enable the quick and easy selection of herbal treatments for various signs and symptoms of illnesses.

Gastroprotective herbs for headache management in Persian medicine: A comprehensive review.

The gut-brain axis is a bidirectional communication system that exists between the brain and gut. Several studies claimed that some types of headaches are associated with various gastrointestinal (GI) disorders. In Persian medicine (PM), physicians believed that gastric disturbances could stimulate headache and introduced some herbs for boosting gastric function as a therapeutic remedy for headache. Here we review the current evidence for the gastroprotective and antiheadache effects of herbs used in PM. Herbs used for their gastrotonic effects in PM were identified from selected Persian medical and pharmaceutical textbooks. PubMed, Scopus and Google Scholar were used to search for contemporary scientific evidence relating to the gastric and neurologic effects of these plants. A total of 24 plants were recorded from the selected sources included in this review, most of which belonged to the Rosaceae family. Phyllanthus emblica, Zingiber officinale, Boswellias errata, Punica granatum and Hypericum perforatum had the most recent studies related to GI disorder and headache, while current research about quince, rose, apple, hawthorn and pear was limited. Reducing Helicobacter pylori growth, gastritis, erosion of the stomach lining, hemorrhage and perforation, improving gastric mucosal resistance, antisecretary, antiulcer, antipyretic, analgesic, sedative, anxiolytic, anti-inflammatory, anticonvulsant, neuroprotective and antioxidant effects as well as improvement in memory scores were some of the gastrotonic and neuroprotective mechanisms described in the current research. These results confirmed that medicinal plants prescribed in PM may improve headache in patients through the management of GI abnormalities. However, further studies are recommended to investigate the efficacy and safety of the mentioned medicinal plants.

Pistacia Genus as a Potential Source of Neuroprotective Natural Products.

Neuroprotective agents are able to defend the central nervous system against acute or chronic neuronal injuries. Even with the progress made over the last decades, most of the medications prescribed for the management of neurodegenerative diseases can only reduce their symptoms and slow down their progression. Based on natural product research, there are potential effective medicinal plants and phytochemicals for modulating neuronal functions and protecting against neurodegeneration. Plants in the genus Pistacia are also among valuable natural resources for neuroprotection research based on experiences in traditional medicine. Studies have supported the value of bioactive compounds of the genus Pistacia for central nervous system disorders such as Alzheimer's, Parkinson's, multiple sclerosis, cerebral ischemia, depression, and anxiety. Related literature has also revealed that most of the evidence on neuroprotection in the genus Pistacia is in the form of preliminary studies, mainly including models of behavior, motor function, and memory impairments in animals, neural toxicity, cerebral ischemia and seizure models, evaluation of their effects on antioxidant and inflammatory biomarkers, amyloid ß aggregation, and acetylcholinesterase as well as investigations into some cellular pathways. Along with the phytonutrients in kernels such as pistachios, various phytochemicals, mostly terpenes, and phenolic compounds have also been identified in different plant parts, in particular their oleoresins, of species in the genus Pistacia. In this review, the pharmacology of neurological effects and related molecular mechanisms of the plants belonging to the genus Pistacia and its active constituents, as well as pharmacokinetics aspects, are discussed.