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It is widely believed that Silybum marianum (Silymarin) alleviates liver injury arising from various etiologies with different degrees of damage through its anti-inflammatory and antioxidant activities. This meta-analysis investigated the effects of silymarin administration on serum levels of liver enzymes including AST, ALT and ALP. From inception to November, 2023, a comprehensive literature search was conducted. Inclusion criteria for this study were randomized trials that provided sufficient data for each group at the beginning and end of the follow-up period. Ultimately, 55 studies with a total of 3545 patients were included. Comprehensive Meta-Analysis (CMA) V4 software was used for meta-analysis. Begg's funnel plot symmetry status, Begg's rank correlation, and Egger's weighted regression tests were used to examine potential publication bias. According to the findings of this meta-analysis silymarin administration showed a significant reduction in AST (SMD [95% CI]: - 0.670 [- 0.931, - 0.408], p- value = 0.000), and ALT (SMD [95% CI]: - 0.912 [- 1.177, - 0.646], p- value = 0.000) levels. While it had no statistically significant effect on ALP level (SMD [95% CI]: - 0.236 [- 1.929, 1.458], p -value = 0.159). Meta-regression analysis showed that there is no significant association between dose, age, BMI, treatment duration and hepatoprotective effects of silymarin. In subgroup analysis, a greater reduction in liver enzymes levels was observed in patients under 50 years old. The subgroup analysis was also showed significant decrease in AST and ALT levels for patients with BMI less than 30, while silymarin treatment had no significant effects on AST and ALT levels in patients with BMI ≥ 30. Silymarin at a dose of less than 400 mg and treatment duration ≤ 2 months showed greater decreasing effects on AST and ALT levels compared to its high doses and longer treatment duration. AST and ALT levels significantly decreased in patients with NAFLD and viral hepatitis, while it had no significant hepatoprotective effects in patients with drugs induced liver injury and alcohol-related liver disease. Modifying the dose and treatment duration with silymarin is recommended in patients with various causes of liver damage. Graphical Abstract

Background Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cholinergic dysfunction, neuroinflammation, oxidative stress, and memory impairment. The Salvia genus has been used since ancient times for its anti-inflammatory and neuroprotective properties. In this study, we aimed to investigate the effects of Salvia aristata hydroalcoholic extract (SAHE) and dichloromethane extract (SADE) on various aspects of memory and AD. Methods Column chromatography was utilized in the phytochemical analysis to isolate and purify bioactive compounds. The structures of the isolated compounds were determined through spectroscopic techniques, including 1D and 2D NMR, along with IR, UV, and HRESIMS for the new compound. Cholinesterase inhibitory activity was assessed using a modified Ellman’s method. Additionally, the antioxidant activity and metal chelation capacity of SAHE and SADE were evaluated using the DPPH assay and spectroscopic methods, respectively. Moreover, the neuroprotective effects in PC12 cells were investigated using the AlamarBlue assay, and the ability to mitigate scopolamine-induced memory impairment in rats was assessed using the Morris water maze (MWM) test. Results In this study, we isolated and structurally elucidated an undescribed compound, namely salvinarin ( 2 ), as well as four known compounds including linariin ( 1 ), pectolinarin ( 3 ), scutellarein 4’-O-methyl-7-O-rutinoside ( 4 ), and 5-O-coumaroylquinic acid ( 5 ) from SAHE for the first time. In vitro analyses revealed that SAHE, SADE, and linariin exhibited significant neuroprotective effects against H 2 O 2 -induced cytotoxicity in PC12 cells. Notably, SAHE demonstrated potent acetylcholinesterase (AChE) inhibition (IC 50  = 322.83 ± 1.11 µ g/mL), significant antioxidant activity (IC 50  = 99.16 ± 1.24 µ g/mL), and strong metal chelating capacity toward Cu 2+ , Zn 2+ , and Fe 2+ . Moreover, oral administration of SAHE (400 mg/kg/day) significantly ameliorated memory impairment induced by scopolamine in a rat model. This improvement was evident in parameters such as traveled distance ( p  < 0.001), escape latency ( p  < 0.001), and time spent in the target quadrant ( p  < 0.01) in the Morris water maze test. Conclusions Considering all findings, including significant neuroprotective, antioxidant, and metal-chelating properties, alongside notable efficacy in enhancing memory in rat models, S. aristata could be a potential candidate for memory improvement. Graphical Abstract

Background According to traditional medicine, Melissa officinalis L., (lemon balm) has been known to remove harmful substances from the blood and is considered a cardiac tonic. Therefore, its use as a cardiovascular remedy may explain the lipid-lowering effects of lemon balm. Dyslipidemia can be considered as a significant preventable risk factor for atherosclerosis, coronary heart disease and type 2 diabetes. The present study is the first meta-analysis to investigate the effects of M. officinalis administration on serum levels of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG) and total cholesterol (TC). Methods From inception to October 2023, a thorough search through literature was conducted using PubMed, Scopus, and Web of Science. The inclusion criteria of this study were randomized controlled trials, with or without blinding which provided adequate data for each group at the beginning and end of the follow-up period. Meta-analysis was performed on randomized controlled trials using Comprehensive Meta-Analysis (CMA) V4 software. Risk of bias in the selected studies was examined according to the revised Cochrane risk-of-bias tool for randomized trials. Begg’s funnel plot symmetry status, Begg’s rank correlation, and Egger’s weighted regression tests were employed to evaluate potential publication bias. Results The meta-analysis comprised of 5 randomized controlled trials with a total of 302 patients. The findings of the meta-analysis indicated that the consumption of lemon balm had a significant decrease in TG (SMD (95% CI): -0.396(-0.620, -0.173), p- value  =  0.001), TC (SMD (95% CI): -0.416 (-0.641, -0.192), p -value < 0.001) and LDL (SMD (95% CI): -0.23(-0.45, -0.008), p  < 0.05) levels compared to the placebo group. While it had no statistically significant effect on HDL level (SMD (95% CI): 0.336(-0.091, 0.767), p -value = 0.123). No significant and detectable publication bias was found in the meta-analysis. Additionally, all included clinical studies demonstrated a low risk of bias for missing outcome data and selection of the reported results. The robustness of the results was demonstrated by a sensitivity analysis using the one-study remove method. Conclusions The findings of this meta-analysis provide evidence that lemon balm may be administered as a safe and beneficial herbal medicine for reducing TC, TG and LDL levels. According to the pooled results of 5 studies with a total of 302 patients, lemon balm intake had no significant effect on HDL level. This study reinforces the notion that lemon balm may have a substantial impact on serum lipid profile as a potential remedy in cases of dyslipidemia. The main concern of our research is the limited number of eligible studies and the relatively small population size of each individual study. The patients of these studies had different types of diseases and metabolic syndromes. However, the meta-analysis was sufficiently powered to detect the considerable effects of lemon balm in the combined population regardless of type of diseases.

Salvia macrosiphon Boiss. is an aromatic perennial herb belonging to the family Lamiaceae. Phytochemical studies and biological activities of this plant have been rarely documented in the literature. The current study aimed to investigate antibacterial and cytotoxic activity of different fractions of aerial parts of S. macrosiphon. Also, we tried to isolate and identify cytotoxic compounds from the plant. In this respect, the hydroalcoholic extract of the corresponding parts of the plant was fractionated into four fractions. Then, antibacterial and cytotoxic activity of each fraction were examined. It was found that the chloroform fraction had a good antibacterial activity against gram-positive and gram-negative bacteria. The most potent cytotoxicity was also obtained by the n-hexane fraction comparing with etoposide as the reference drug which was selected for the study and characterization of secondary metabolites. Accordingly, 13-epi manoyl oxide (1), 6α-hydroxy-13-epimanoyl oxide (2), 5-hydroxy-7,4'-dimethoxyflavone (3), and β-sitosterol (4) were isolated and evaluated for their cytotoxic activity. Among them, compound 1 revealed significant cytotoxicity against A549, MCF-7, and MDA-MB-231. It merits mentioning that it showed high selectivity index ratio regarding the low cytotoxic effects on Human Dermal Fibroblast which can be considered as a promising anticancer candidate.

Pistacia, a genus of flowering plants from the family Anacardiaceae, contains about twenty species, among them five are more popular including P. vera, P. atlantica, P. terebinthus, P. khinjuk, and P. lentiscus. Different parts of these species have been used in traditional medicine for various purposes like tonic, aphrodisiac, antiseptic, antihypertensive and management of dental, gastrointestinal, liver, urinary tract, and respiratory tract disorders. Scientific findings also revealed the wide pharmacological activities from various parts of these species, such as antioxidant, antimicrobial, antiviral, anticholinesterase, anti-inflammatory, antinociceptive, antidiabetic, antitumor, antihyperlipidemic, antiatherosclerotic, and hepatoprotective activities and also their beneficial effects in gastrointestinal disorders. Various types of phytochemical constituents like terpenoids, phenolic compounds, fatty acids, and sterols have also been isolated and identified from different parts of Pistacia species. The present review summarizes comprehensive information concerning ethnomedicinal uses, phytochemistry, and pharmacological activities of the five mentioned Pistacia species.

Medicinal plants cultivation, provides required resources and makes avoidance of wild resources depletion, furthermore it may control the growing condition, harvesting at the right time, and reducing the possibility of adulteration.1 There are several studies on the chemotype development in various plants' cultivars and differences in essential oils composition and biological activities between the cultivated and wild ones.2-7 The research implemented by Chatzopoulou et al., has shown the same major components in both wild and cultivated Hypericum perforatum L., however there was significant difference in the amount of main components.4 Bunium persicum (Boiss.) B. Fedtsch (Apiaceae) is a perennial herb, native to Iran, Pakistan and Afghanistan.8 The small odorant fruits of B. persicum (\"Zireh siah\" or \"Wild Caraway\") are traditionally used as antiseptic, carminative and condiment.9 Unfortunately, due to climate changes and indiscriminate harvesting of the whole plant instead of collecting fruits, this invaluable species has become an endangered species.10 Several studies have previously determined essential oil composition of B. persicum and commonly reported y-terpinene, cuminaldéhyde and p-cymene as major compounds.11-14 Moreover, the oil has demonstrated strong antibacterial activity against some gram positive and gram negative bacteria and also considerable insecticide effects.14,15 Another research has investigated the essential oil composition of wild and cultivated B. persicum from India and shown some similarities and differences in oils, mainly the higher level of cuminaldehyde in cultivated fruits.6 In a study exploring antioxidant components of the fruits, kaempferol, caffeic acid and p-coumaric acid were introduced as active ingredients from extract.16 Also, antimicrobial properties of these three compounds against some bacterial and fungal strains have been shown in some studies.17-20 In recent years, B. persicum is cultivated in limited areas in Iran especially in Khorasan Razavi province. According to our results, the wild grown essential oil showed higher inhibitory activity on microorganisms, while only a slight difference was determined in essential oil major compounds such as the level of p-cymene and y-terpinene.

Using Lawsonia inermis L. (henna) seeds has been frequently recommended for the improvement of memory in Iranian Traditional Medicine (ITM). In this respect, different fractions of the plant were prepared and evaluated for their in vitro biological assays related to Alzheimer’s disease (AD), including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity as well as metal chelating ability and DPPH antioxidant activity. The dichloromethane and ethyl acetate fractions were able to inhibit the BChE selectively with IC50 values of 113.47 and 124.90 μg/mL, respectively, compared with donepezil as the reference drug (IC50 = 1.52 μg/mL). However, all fractions were inactive toward AChE. Phytochemical analysis of the dichloromethane fraction indicated the presence of β-sitosterol (1), 3-O-β-acetyloleanolic acid (2), 3-O-(Z)-coumaroyl oleanolic acid (3), betulinic acid (4), and oleanolic acid (5). The inhibitory activity of isolated compounds was also evaluated toward AChE and BChE. Among them, compounds 2 and 5 showed potent inhibitory activity toward BChE with IC50 values of 77.13 and 72.20 μM, respectively. However, all compounds were inactive toward AChE. Moreover, molecular docking study confirmed desired interactions between those compounds and the BChE active site. The ability of fractions and compounds to chelate biometals (Cu2+, Fe2+, and Zn2+) was also investigated. Finally, DPPH antioxidant assay revealed that the ethyl acetate (IC50 = 3.08 μg/mL) and methanol (IC50 = 3.64 μg/mL) fractions possessed excellent antioxidant activity in comparison to BHA as the positive control (IC50 = 3.79 μg/mL).

In the study, anti- Candida activity and phenol contents of Lythrum salicaria L. calli and wild species have been evaluated. The seeds of L. salicaria (Lythraceae), collected from Lahidjan City in the north of Iran, were cultured in Murashige and Skoog medium (MSM) with a supplement, gibberellin, to germinate. Callus inductions were performed from segments of seedling on MSM containing different concentrations of plant growth regulators, 2,4-dichlorophenoxyacetic acid (2,4-D) and 6-benzylaminopurine (BAP). The activity of calluses extracts, wild plant, gallic acid, and 3,3′,4′-tri-O-methylellagic acid-4-O-β- d -glucopyranoside (TMEG) as the main phenolic compounds against Candida albicans was assessed using cup plate diffusion method. The total phenols contents of calli and wild plant extracts were analyzed using Folin–Ciocalteu reagent. The callus formation in MSM supplemented with various concentrations of 2,4-D and BAP were 0–100 %. Anti- Candida activity of callus extract which obtained from MSM supplemented with 2,4-D and BAP (1 mg dm −3 ) was similar to the wild plant extract. Minimum inhibitory concentration values of gallic acid and TMEG were obtained as 0.312 and 2.5 mg cm −3 , respectively. Gallic acid equivalent values in all treatments were from 0 to 288 μg GAE mg −1 . Phenolic contents of plant aerial parts (331 ± 3.7 μg GAE mg −1 ) and the callus, which developed in MSM including 1 mg dm −3 of both 2,4-D and BAP, showed the same phenolic value and exhibited anti- Candida extract activity.

Foeniculum vulgare Mill. (F. vulgare), commonly known as Fennel, is a popular medicinal plant with various pharmacological activities mentioned in traditional Iranian medicine (TIM) and modern phytotherapy such as antioxidant, cytotoxic, anti-inflammatory, antimicrobial, bronchodilatory, estrogenic, diuretic, lithontripic, galactogogue, emmenagogue, antithrombotic, hypotensive, gastroprotective, hepatoprotective, memory enhancing, and antimutagenic activities. No serious adverse events were recorded after ingestion of F. vulgare except some cases of allergic reactions. The estrogenic activity of F. vulgare brings some side effects such as decrease in protein concentration and acid and alkaline phosphatase in male genital organs, increase in weight of mammary glands and reproductive organs in women and premature thelarche in girls. However, no evidence of teratogenicity was recorded, it is better not to use F. vulgare during pregnancy due to its estrogenic activity. Because of inhibition of cytochrome P450 3A4 (CYP3A4), the pharmacokinetic parameters of drugs mainly metabolized by this isozyme may be affected by F. vulgare. In addition, a significant interaction between cyprofloxacin and F. vulgare was demonstrated. The aim of current paper is to review pharmacological properties, toxicity and adverse events, and drug interactions of vulgare and brings conclusive results about the use of this plant in men, women and during pregnancy.

BackgroundTrachyspermum ammi (L.) Sprague is used for treating gastrointestinal disorders. Several studies indicated gastric antiulcer activity of T. ammi extract, yet the effect of its essential oil has not been studied on.ObjectivesThe present study evaluates chemical composition of T. ammi essential oil and anti-peptic ulcer effect of the essential oil as well as its three major components in ethanol induced-gastric ulcers in rats.MethodsPrimarily chemical composition of the essential oil was analyzed by gas chromatography-mass spectrometry (GC/MS). Rats received the essential oil (500, 250, 125, 62.5, 31.25 mg/kg), thymol (30, 100 mg/kg), para-cymene (100, 150 mg/kg) and gamma-terpinene (100, 150 mg/kg) using gavage tube along with ethanol 80%. Finally, dissected stomachs were assessed both macroscopically and microscopically to evaluate anti-ulcerative effect of the essential oil and the pure compounds. Moreover, molecular docking was utilized to explore the interactive behavior of the main components with active site residues of H+/K+ ATPase.ResultsAnalysis of the essential oil indicated that para-cymene (37.18%), gamma-terpinene (35.36%) and thymol (20.51%) are the main components. Administration of different doses of the essential oil noticeably diminished the number of peptic ulcers in a dose-dependent manner. Among the main components, thymol was more potent than para-cymene and gamma-terpinene. Administration of the essential oil (500 mg/kg) and thymol (100 mg/kg) observed maximum inhibition percentage (98.58% and 79.37%, respectively). Molecular docking study provides the evidence of thymol ability to inhibit H+/K+ ATPase.ConclusionsThe findings revealed that T. ammi essential oil can be applied to treat gastric ulcer as a natural agent.[Images not available. See PDF.]Graphical abstract