Therapeutic effects of saffron (Crocus sativus L) on female reproductive system disorders: A systematic review.

The effect of Crocus sativus on several disorders has been discussed or even confirmed, but the efficacy of this herb on the female reproductive system has not been well presented. In this regard, this systematic review comprehensively discussed the efficacy of C. sativus and its main phytochemical compounds on the female reproductive system and its disorders for the first time. In this systematic review, scientific databases, including PubMed, Web of Sciences, Google Scholar, Scopus, and Scientific Information Database, were explored profoundly. In vivo, in vitro, and human studies published until the end of July 2023, which had investigated the pharmacological properties of C. sativus, crocin, crocetin, safranal, or picrocrocin on the female reproductive system, were selected. A total of 50 studies conducted on the effect of C. sativus on the female reproductive system were acquired. These studies confirmed the efficacy of C. sativus or its main phytochemical ingredients in several aspects of the female reproductive system, including regulation of sex hormones, folliculogenesis, ovulation, and protection of the ovary and uterus against several oxidative stress. Several retrieved studies indicated that this herb also can alleviate the symptoms of patients suffering from dysmenorrhea, premenstrual syndrome, menopause, polycystic ovary disease (PCOD), and sexual dysfunction. Furthermore, it is a promising candidate for future studies or even trials regarding ovarian and cervical cancers. This review concluded that C. sativus can improve the symptoms of several female reproductive system disorders, which is particularly due to the presence of phytochemical ingredients, such as crocin, crocetin, and safranal.

Hydroalcoholic extract of Passiflora incarnata improves the autistic-like behavior and neuronal damage in a valproic acid-induced rat model of autism.

Experimental autism in rodents can be caused by prenatal valproic acid (VPA) exposure. Some diseases, such as attention-deficit hyperactivity disorder (ADHD), insomnia, opiate withdrawal, and generalized anxiety disorder can be treated by consuming Passiflora incarnata, due to the possession of bioactive compounds like alkaloids, phenols, and flavonoids. The present study aims to investigate the role of the hydroalcoholic extract of Passiflora incarnata in behavioral and oxidative stress aberrations induced by VPA. On the gestational day (GD), 12.5, pregnant Wistar rats received VPA (600 mg/kg subcutaneously). Male pups were treated with the extract (30,100, and 300 mg/kg) from postnatal day 35 to the end of the experiment, and underwent behavioral testing to evaluate locomotion, repetitive, and stereotyped movements, anxiety, and social and cognitive behaviors. After behavioral testing, the blood sample was taken from the left ventricle to determine serum catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA), and total antioxidant capacity (TAC). Then the animals were euthanized and their brains were taken out for histological assays of the prefrontal cortex (PFC) and CA1 hippocampus with hematoxylin/eosin. The total phenol and flavonoid content and antioxidant activity of the extract were also measured. A significant improvement was observed in behavioral disturbances, particularly with 300 mg/kg of Passiflora. Moreover, the formation of oxidative stress markers significantly decreased at this dose. The extract also reduced the percentage of damaged cells in the CA1 and PFC. The results indicated that Passiflora extract could ameliorate VPA-induced behavioral aberrations possibly due to the antioxidant actions of its bioactive compounds.

Efficacy and Safety of a Persian Medicine Formula on Functional Dyspepsia Symptoms: A Randomized Double-Blind Active-Control Clinical Trial.

INTRODUCTION: Functional dyspepsia (FD) is one of the most frequent gastrointestinal disorders with a high burden. Although FD is a heterogeneous disorder without any standard therapy (treatment/treatment - repetition), there is a wide history of using herbal remedies for its treatment. Two of these herbal remedies quoted in various Persian medicine resources are celery and ajwain. Their effects have been investigated in recent clinical trials in FD patients. We aimed to compare the effect of celery and ajwain to that of domperidone in patients with postprandial distress syndrome. METHODS: This is a randomized double-blind active-control clinical trial, conducted at Kerman, Iran in 2020. Participants of this study were 100 patients suffering from FD (postprandial distress syndrome subtype). The intervention group received 1 g of the combination of celery and ajwain (Apium graveolens L. and Trachyspermum copticum [L.] Link), while the control group received 30 mg of domperidone per day for 4 consecutive weeks. Primary outcomes were symptom severity and frequency, and secondary outcomes were quality of life (QoL) and safety. All outcomes were assessed at the end of the trial and also 4 weeks after the trial was finished. RESULTS: No significant differences in symptom frequency were found between groups. However, differences in symptom severity were found at the end of the follow-up (week 8) (p = 0.001). The intragroup analysis showed a significant decrease in the symptoms severity and frequency at the end of week 4 in both groups (p < 0.001). QoL in the intervention group was higher compared to the control group at the end of the study (p < 0.001) and at the point of the follow-up (week 8; p < 0.001). No serious adverse events occurred in either group. CONCLUSION: The herbal mixture of celery and ajwain could be considered a safe and effective remedy, decreasing the severity of symptoms and increasing QoL in patients with postprandial distress syndrome. It is further suggested to confirm these findings in high-quality multi-center clinical trials.

Effects of the Ethanol and Ethyl Acetate Extracts of Terminalia chebula Retz. on Proliferation, Migration, and HIF-1α and CXCR-4 Expression in MCF-7 Cells: an In Vitro Study.

Over recent years, much attention has been devoted to the field of screening natural products and/or their novel structures because of reversing cancer progression. The current research work was intended to explore the cytotoxic activity of ethanol and ethyl acetate extracts of dried fruit of Terminalia chebula Retz. (T. chebula) in MCF-7 cell line. High-performance thin-layer chromatographic (HPTLC) method and Folin-Ciocalteu colorimetric techniques were performed. Anti-proliferative activities of T. chebula fruit extracts on the MCF-7 cell line were evaluated using MTT assay. Effects of both extracts on the migration of MCF-7 cells and the size of MCF-7-derived spheroids were also evaluated. Moreover, antioxidant properties were measured by DPPH and FRAP methods. Western blotting was used to measure the HIF-1α and CXCR-4 protein levels. Chebulagic acid, gallic acid, chebulinic acid, and ellagic acid were found as major compounds in both extracts. The total phenolic contents based on gallic acid equivalent (GAE) in the ethanol and ethyl acetate extracts of T. chebula were found to be 453.68 ± 0.31 and 495.12 ± 0.43 mg GAE/g dry weight of the extract, respectively. Both extracts exerted a significant dose- and time-dependent cytotoxicity effect on MCF-7 cells. They also had a marked negative effect on the average size of MCF-7-derived spheroids and their migration rate. None of the extracts exhibited stronger antioxidant activities than vitamin C. Furthermore, both extracts at a concentration of 125 µg/ml could meaningfully decrease the expression levels of HIF-1α and CXCR-4 in MCF-7 cells. These data represent that T. chebula may be a valuable medicinal resource in the regulation of breast cancer proliferation, growth, and metastasis.

Characteristics and in vitro anti skin aging activity and UV radiation protection of morin loaded in niosomes.

BACKGROUND: One of the dermatologic problems in elderly people is skin aging, which is a natural and complex biological process. Morin is a flavonoid with high radical scavenging activity as well as antityrosinase effects but its low water solubility has restricted its application. AIMS: This research aimed to develop, characterize, and optimize morin niosomes composed of non-ionic surfactants, and evaluate the in vitro UV protection and antiaging effectiveness. METHODS: Niosomes were prepared by the film hydration method with sorbitan monostearate (Span® 40), polyoxyethylenesorbitan monopalmitate (Tween® 40), and cholesterol. The niosomes were characterized in terms of size, zeta potential, morphology, in vitro release behavior, and drug entrapment efficiency (EE). Afterward, antiaging activity, including antityrosinase, antioxidant, intracellular reactive oxygen species (ROS) scavenging, and sun protection factor (SPF) were evaluated. RESULTS: The optimized niosomes appeared as unilamellar vesicles with a spherical shape, with size, zeta potential, and EE values of 6.13 ± 0.40 µm, -0.81 ± 0.32 mV, and 89.35% ± 2.80%, respectively. The noisome formulation remained stable at -4°C for 3 months. The release profiles of morin loaded in niosomes revealed the extended release over 8 h and followed zero-order release kinetics. Morin-loaded niosomes exhibited no significant toxicity toward the L929 cell line. The niosome loaded with morin showed anti skin aging activity, including antityrosinase effects (IC50 = 13.17 ± 1.58 µg/ml), antioxidant (IC50 = 28.49 ± 2.05 µg/ml), and ROS scavenging activity. For 1% and 5% (w/w) morin niosomes in eucerin base cream, the SPF was 39.03 ± 1.01 and 38.15 ± 0.82, respectively, whereas the noisome-free morin cream exhibited an SPF of 4.47 ± 0.56. CONCLUSION: Morin-loaded niosome has been shown to provide sun protection and antiaging effects, suggesting that it could be used in pharmaceutical and cosmetic products.

Efficacy of the herbal formula of Foeniculum vulgare and Rosa damascena on elderly patients with functional constipation: A double-blind randomized controlled trial.

BACKGROUND: Constipation is a common chronic bowel disorder with an incidence of more than 50% in the elderly population. Complementary and alternative medicine is a cost-effective and satisfactory treatment for constipation used widely by the elderly. OBJECTIVE: This study evaluates the efficacy of an herbal formula made from Foeniculum vulgare Mill. and Rosa damascena for the treatment of constipation in an elderly population and consequent changes to their quality of life. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This double-blind randomized active controlled clinical trial, with parallel group allocation ratio of 1:1, was conducted in a referral clinic in Afzalipour Hospital, affiliated to Kerman University of Medical Sciences in Kerman, Southeastern Iran. Individuals over 60 years of age, diagnosed with functional constipation (based on the Rome IV criteria), were included in this study. Participants received a sachet of 10 g F. vulgare and R. damascena (herbal formula group) or polyethylene glycol 4000 (PEG 4000 group) with a glass of warm water two times a day for 4 weeks and were followed up for 4 additional weeks. MAIN OUTCOME MEASURES: Constipation severity, stool consistency, and the quality of life were used as the primary outcomes. Drug side effects were used as a secondary outcome. The outcomes were assessed using the Constipation Assessment Scale, the Bristol Stool Form Scale, and the Patient Assessment of Constipation Quality of Life questionnaire. RESULTS: A total of 25 participants in each group completed the four-week treatment cycle and the eight-week follow-up. At the end of the four-week treatment cycle, all clinical outcomes had significant improvements in both groups (P < 0.05). The analysis of constipation severity (P < 0.001), stool consistency (P < 0.001), and the quality of life (P < 0.001) showed significant improvements with fewer side effects (mild diarrhea) and a longer duration of symptom relief in the herbal formula group compared to the PEG 4000 group. CONCLUSION: Although both interventions significantly improved the treatment outcomes, constipation severity, stool consistency and the quality of life were improved more effectively by the herbal formula than by PEG 4000; however, the mechanism of action is not yet understood. TRIAL REGISTRATION: This trial was registered in the Iranian Registry of Clinical Trials (IRCTID: IRCT20200108046056N1).

The efficacy of henna (Lawsonia inermis L.) mouthwash versus chlorhexidine gluconate 0.2% mouthwash as adjuvant therapy of oral lichen planus: A randomized double-blind clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: In modern medicine, some traditional remedies are introduced to be effective in treatment. Accordingly, the henna plant (Lawsonia inermis L.) is studied more than before. Previous studies have shown many medical properties for henna, such as anti-inflammatory and anti-fungal properties. AIM OF THE STUDY: Oral lichen planus (OLP) is a common mucocutaneous disease with chronic immunomodulatory disruptions. Topical corticosteroids are the first line of OLP treatment. Previous studies have suggested different adjunctive therapies for preventing the side effects of corticosteroids overuse. This study aimed to compare the effects of henna and chlorhexidine mouthwashes as adjunctive therapy. MATERIALS AND METHODS: This parallel-group, double-blind, randomized controlled study was conducted on forty OLP patients. Luteolin content was determined in Henna mouthwash composed of 2% aqueous extract of henna, 2% ethanol, 10% glycerol, and 0.1% methylparaben distilled water. Henna or chlorhexidine mouthwashes were prescribed twice daily as an adjuvant to the topical corticosteroid treatment. Visual analog scale (VAS) index and Thongprasom rating were used to measure pain intensity and clinical signs of patients at days 0,7, and 14. The collected data were analyzed using SPSS software (version 26.0; SPSS). Ordinal logistic regression was used to investigate the effect of independent variables on Thongprasom and VAS scores. RESULTS: In this clinical trial, 82.6% of the participants were women. There was no difference between the two study groups in terms of VAS scores (p = 0.404) and clinical features (p = 0.305) in the second follow-up visit. All drug regimens caused clinical signs and symptoms relief. CONCLUSIONS: There was no significant difference between the groups receiving topical corticosteroid supplementation, neither henna mouthwash nor chlorhexidine mouthwash. The therapeutic effects of henna mouthwash in the main or adjuvant treatment of OLP need more evaluation in future research. Henna mouthwash can be a good alternative to chlorhexidine mouthwash if no side effects are reported.

Efficacy of Herbal Based Syrup on male sexual experiences: A double-blind randomized clinical trial.

BACKGROUND AND AIM: An Aphrodisiac includes any drug and food that arouses sexual instinct, induces venereal desire, and increases pleasure and performance. The present study was designed to clinically evaluate efficacy and safety of Herbal Based Syrup (HBS) composed of Tribulus terrestris L., Panax ginseng C.A. Meyer., Zingiber officinale Rosc, Ceratonia siliqua L., Papaver rhoeas L., and Palm tree pollen on sexual experience of men. EXPERIMENTAL PROCEDURE: The study was designed as a double-blind randomized clinical trial. The main outcome measures were the responses obtained from using the Arizona Sexual Experience Scale (ASEX). The ASEX was completed by 100 married and seemingly healthy men before and after taking one dose of HBS or placebo and at least one sexual intercourse. In addition, possible side effects were observed. A split-plot ANOVA (SPANOVA) design was used for statistical analysis. RESULTS: Results of analysis of data for each variable of the ASEX showed significantly lower scores in HBS-treated group compared to the placebo (control) group in items of desire, arousal, erection, orgasm and satisfaction (p < 0.05). No drug-related serious adverse events were observed. CONCLUSION: Results of this study indicated a significant improvement in sexual experience of men following consumption of HBS. Due to various complications reported about the use of chemical sexual drive enhancers, HBS can be introduced as an alternative with fewer side effects.

Effects of a Plantago ovata-based herbal compound in prevention and treatment of oral mucositis in patients with breast cancer receiving chemotherapy: A double-blind, randomized, controlled crossover trial.

BACKGROUND: Oral mucositis (OM) is one of the most common complications of mucotoxic cancer therapy. Mucositis induces clinically significant pain, increases the risk of infections and affects the patients' quality of life. OBJECTIVE: This study investigated the effects of an herbal preparation from Plantago ovata hydrocolloid in the prevention and treatment of OM, in breast cancer patients undergoing chemotherapy with a regimen including adriamycin. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: This research was a double-blind, randomized, controlled crossover trial. The herbal compound consisted of a mixture of 500 mg of P. ovate husk in 30 mL water plus three drops of vinegar per dose, which was used as a mouthwash. Phytochemical and physicochemical tests of the compound were also performed. Twenty-eight patients who developed mucositis during the chemotherapy screening cycle were randomized to the herbal compound (n = 14) and placebo (n = 14) groups. They received herbal compound or placebo three times per day during their next chemotherapy cycle (cycle 1 of treatment). Patients were crossed over during cycle 2 of treatment and received the alternative therapy. An oral care protocol was prescribed to all patients in cycles 1 and 2 of the treatment. MAIN OUTCOME MEASURES: The patients were visited at baseline, the end of the first and second weeks of the screening cycle, and the end of the first and second weeks of each of two treatment cycles. The degree of mucositis was used as the main treatment outcome. Other indexes, such as the severity of pain, xerostomia grade and the quality of life were also measured. RESULTS: Compared with the placebo, the herbal compound significantly reduced the degree of mucositis, the severity of pain and the xerostomia grade; it also improved the patients' quality of life (P < 0.05). Comparison between the screening cycle and placebo treatment group showed that the oral care protocol had a significant effect in the reduction of OM (P < 0.05). CONCLUSION: The oral care protocol and the herbal compound based on P. ovata are effective ways for preventing and treating OM in patients undergoing mucotoxic cancer therapy. TRIAL REGISTRATION: Iranian registry of clinical trials IRCT20180923041093N1.

The efficacy of a traditional medicine preparation on second-degree burn wounds in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lime Salve (L.S) has been well documented from the 9th to the 19th century AD by traditional Iranian medicine (TIM) as an effective remedy for burn healing. AIM OF THE STUDY: The present study was undertaken to evaluate the healing effect and related underlying mechanisms of Lime Salve in a model of deep second-degree thermal burn in male Wistar rats. MATERIALS AND METHOD: L.S was made up of a combination of refined calcium hydroxide powder, beeswax and sesame oil and its quality control was assessed. A deep second-degree burn was created by a hot plate in 48 male Wistar rats. Afterwards, they were randomly divided into four groups including normal saline (C group), L.S (T group), basement of formulation composed of beeswax and sesame oil (B group) and silver sulfadiazine (S group). On days 5, 10, 17 and 24, the wounds were digitally photographed by a camera and after sacrifice of the rats, skin samples were obtained for performing qRT-PCR, immunohistochemistry staining and histological examination. RESULTS: L.S prominently augmented the wound closure rate, neovascularization on day 10 and collagen formation on days 17 and 24 in comparison with the C group. Furthermore, the Salve-exposed specimens showed a significant higher epithelialization during the experiment with a peak on day 24. qRT-PCR also showed that on day 10, VEGF and TGF-ß1 genes were significantly higher in the T group as compared with the C group. Also, MMP-9 and MMP-2 genes had a significant peak of expression on day 17 and rapid reduction of expression on day 24. Expression levels of IL-6 and TNF-α genes peaked on day 10 in the T group, followed by a progressive reduction until the end of the examination. CONCLUSION: L.S could effectively accelerate the healing process of deep second-degree burn wounds and therefore, it may be recommended as a promising topical medication for treating burn wounds in the future clinical trials.

Phytoniosome: a Novel Drug Delivery for Myrtle Extract.

Traditionally, Myrtus communis (myrtle) has been used for treatment of several kinds of disorders. However, there are some factors, namely, low solubility and permeability, which restrict use of myrtle extract (ME) in medical applications. Regarding these limitations, the aim of the present study was to develop a new niosomal formulation to enhance ME stability and permeability. Briefly, several niosomal formulations were prepared by non-ionic surfactants and cholesterol with different molar ratios. Afterward, size, entrapment efficiency (EE%), release and stability of niosomal myrtle extract (nME) were investigated. The effect of ME and nME on viability of 3T3 cells was evaluated using MTT assay. Antibacterial activity of ME and nME was also assessed against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Micrococcus luteus, and Bacillus subtilis. Sizes of niosomes were 5.3 ± 0.3 to 15.9 ± 2.2 µm with 4.1 ± 0.3 to 26.9 ± 1.7 mV zeta potential. The EE% of niosomes was varied from 45.4% to 93.4%. An in-vitro release study on F5 formulation (Span60: Tween60: cholesterol (3:3:4 molar ratio)) revealed that about 36.9%, 38.5% and 26.7% of phytoconstituents were released within 12 h from acetate cellulose membrane, 0.45 µm, regenerated cellulose membrane, 0.45 µm, and cellophane dialysis sack, 12000 Da, respectively. F5 formulation significantly showed lower toxicity on cells. It had higher antibacterial activity that has been shown by lower MICs and higher zone of inhibition compared to ME. Overall, F5 formulation in the presence of 4% ME produced stable multi lamellar vesicles with optimal in-vitro release and EE%. This formulation also exhibited better antibacterial activity than ME.

Development, physicochemical characterization, and antimicrobial evaluation of niosomal myrtle essential oil.

Myrtus communis (myrtle) is well known for its therapeutic effects pertaining to the major secondary metabolites including essential oils (EOs). EOs are composed of volatile compounds and simply evaporate or decompose leading to their instability. Preparation of EOs niosomal formulation may be a promising approach to deal with these obstacles. Niosomal formulations of myrtle essential oil (nMEO) were provided using non-ionic surfactants and cholesterol (Chol). In the next steps, vesicle size, zeta potential, percentage of entrapment efficiency (EE%) and physical stability of nMEO were investigated. Finally, the effect of myrtle essential oil (MEO) and nMEO on microbial growth inhibition were assessed. Values for nMEO size and zeta potential ranged from 6.17 ± 0.32 to 7.24 ± 0.61 (µm) and -20.41 ± 0.17 to -31.75 ± 0.45 (mV), respectively. Higher degrees of EE% were obtained by F6 formulation (Span/Tween 60:Chol (50:50 molar ratio)). Moreover, niosomes have been reported to be stable at 4 °C during a three-month time period. It was revealed that nMEO F6 formulation inhibited growth of Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens, and Bacillus subtilis at concentrations lower than that of MEO. Overall, it was found that stable multilamellar vesicles were formed in the presence of 0.5% MEO and F6 formulation. This formulation also exhibited better antibacterial activity than MEO.

Medicinal Herbs Affecting Gray Hair in Iranian Traditional Medicine.

BACKGROUND: The presence of hair plays an important role in people's overall physical appearance and self-perception. As a result of increased life expectancy, the desire to look youthful plays a bigger role than ever.The use of medicinal plants is as old as mankind and the market will face many new products containing natural oils and herbs in coming years. In traditional Iranian medicine, many plants and herbal formulations are reported for hair growth as well as the improvement in hair quality. The aim of this article is to introduce effective medicinal plants in traditional Iranian medicine to prevent gray hair and advocate them as the new products. METHODS: The present investigation is an overview study and has been codified by library search in the main sources of traditional Iranian medicine. RESULTS: In traditional Iranian medicine, three types of formulations are proposed to prevent gray hair, namely (i) treatment compounds, (ii) preventive compounds, and (iii) hair dyes to color gray hairs. Our search showed that the main parts of a plant that is used in the treatment and preventive compounds are seeds and fruits. These are primarily in the form of topical oil or oral compound (electuary). The majority of plant parts used in hair dyes is from the fruit and/or leaves. CONCLUSION: Natural products are highly popular and the use of plant extracts in formulations is on the rise. This is because synthetic based product may cause health hazards with several side effects. Considering the increased popularity of herbal drugs in hair care, it is worthwhile to conduct systemic investigation on the production and efficacy of these drugs. We trust that our investigation would encourage the use of traditional Iranian medicine in future hair care products.