Effects of Melissa officinalis (lemon balm) consumption on serum lipid profile: a meta-analysis of randomized controlled trials.

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.

Efficacy of ergosterol peroxide obtained from the endophytic fungus Acrophialophora jodhpurensis against Rhizoctonia solani.

AIM: To investigate antifungal activity of the extract and major metabolite of the endophytic fungus Acrophialophora jodhpurensis (belonging to Chaetomiaceae) against crown and root rot caused by Rhizoctonia solani (teleomorph: Thanatephorus cucumeris), as an important pathogen of tomato. METHODS AND RESULTS: The endophytic fungus A. jodhpurensis, has high inhibitory effect against R. solani AG4-HG II in vitro and in vivo. The media conditions were optimized for production of the endophyte's metabolites. The highest amounts of secondary metabolites were produced at pH 7, 30°C temperature, and in the presence of 0.5% glucose, 0.033% sodium nitrate, and 1 gl-1 asparagine as the best carbon, nitrogen, and amino acid sources, respectively. The mycelia were extracted by methanol and the obtained extract was submitted to various chromatography techniques. Phytochemical analysis via thin-layer chromatography (TLC) and nuclear magnetic resonance (NMR) spectroscopy showed that ergosterol peroxide was the major component in the extract of this endophyte. Antifungal activities of the methanolic extract and ergosterol peroxide in the culture media were studied against R. solani. Minimum inhibitory concentrations of the extract and ergosterol peroxide against the pathogen were 600 and 150 µg ml-1, respectively. Ergosterol peroxide revealed destructive effects on the pathogen structures in microscopic analyses and induced sclerotia production. Histochemical analyses revealed that it induced apoptosis in the mycelia of R. solani via superoxide production and cell death. Application of ergosterol peroxide in the leaf disc assay reduced the disease severity in tomato leaves. CONCLUSIONS: Antifungal metabolites produced by A. jodhpurensis, such as ergosterol peroxide, are capable of controlling destructive Rhizoctonia diseases on tomato.

Conferone, a coumarin from Ferula flabelliloba, induced toxic effects on adult T-cell leukemia/lymphoma cells.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is a lymphoid malignancy caused by HTLV-1 infection, with distinct geographical distribution. Despite advances in cancer treatment, the average survival rate of ATL is low. Conferone is a natural coumarin extracted from Ferula species with a wide range of pharmaceutical effects. In search for a novel chemotherapeutic agent, we investigated the cytotoxicity of conferone on ATL cells. METHODS: To obtain conferone, the methanolic extract of the roots of F. flabelliloba was subjected to silica gel column chromatography, followed by 1H- and 13C-NMR to confirm its structure. For cytotoxicity assay, MT-2 cells were treated with different concentrations of conferone (2.5, 5, 10, 20, and 40 µM) for 24, 48, and 72 h, and viability was evaluated by a colorimetric assay using alamarBlue. Cell cycle was analyzed by PI staining and flow cytometry, and qPCR was used to study the expression of candidate genes. RESULTS AND CONCLUSION: Obtained findings indicated that conferone induced considerable cytotoxic effects on MT-2 cells in a time- and dose-dependent manner. In addition, accumulation of cells in the sub-G1 phase of the cell cycle was detected upon conferone administration. Moreover, conferone reduced the expression of CDK6, c-MYC, CFLIPL, and NF-κB (Rel-A) in MT-2 cells. Accordingly, conferone could be considered as a potent agent against ATL, although complementary investigations are required to define more precisely its mechanism of action.

Curcumin-loaded mesoporous silica nanoparticles for drug delivery: synthesis, biological assays and therapeutic potential - a review.

Curcumin-loaded mesoporous silica nanoparticles (MSNs) have shown promise as drug delivery systems to address the limited pharmacokinetic characteristics of curcumin. Functionalization with folic acid and PEGylation enhance anticancer activity, biocompatibility, stability, and permeability. Co-delivery with other drugs results in synergistically enhanced cytotoxic activity. Environment-responsive MSNs prevent undesirable drug leakage and increase selectivity towards target tissues. This review summarizes the methods of Cur-loaded MSN synthesis and functionalization and their application in various diseases, and also highlights the potential of Cur-loaded MSNs as a promising drug delivery system.

Oral Administration Evaluation of the Hydro-Ethanolic Extract of Ginger (Rhizome of Zingiber officinale) against Postoperative-Induced Peritoneal Adhesion: Investigating the Role of Anti-Inflammatory and Antioxidative Effects.

Peritoneal adhesions (PAs) occur and develop after abdominal surgery. Abdominal adhesions are common and often develop after abdominal surgery. Currently, there are no effective targeted pharmacotherapies for treating adhesive disease. In this regard, ginger is wildly used in traditional medicine because of its anti-inflammatory and antioxidant effects and has been investigated for peritoneal adhesion treatment. This study analyzed ginger ethanolic extraction via HPLC to have a 6-gingerol concentration. Four groups induced peritoneal adhesion to evaluate ginger's effects on peritoneal adhesion. Then, ginger extract (50, 150, and 450 mg/kg) was administered by gavage in various groups of male Wistar rats (220 ± 20 g, 6-8 weeks). After scarifying the animals for biological assessment, macroscopic and microscopic parameters were determined via scoring systems and immunoassays in the peritoneal lavage fluid. Next, the adhesion scores and interleukin IL-6, IL-10, tumor necrosis factor-(TNF-) α, transforming growth factor-(TGF-) ß1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were elevated in the control group. The results showed that ginger extract (450 mg/kg) notably decreased inflammatory (IL-6 and TNF-α), fibrosis (TGF-ß1), anti-inflammatory cytokine (IL-10), angiogenesis (VEGF), and oxidative (MDA) factors, while increased antioxidant factor glutathione (GSH), compared to the control group. These findings suggest that a hydro-alcoholic extract of ginger is a potentially novel therapeutic strategy for inhibiting adhesion formation. Also, it might be considered a beneficial anti-inflammatory or antifibrosis herbal medicine in clinical trials. However, further clinical studies are required to approve the effectiveness of ginger.

Peritoneal lavage with Glycyrrhiza glabra is effective in preventing peritoneal adhesion in a rat model.

BACKGROUND: Intraperitoneal adhesion formation is a significant problem following surgeries, resulting in substantial clinical and economic consequences. Glycyrrhiza glabra has several pharmacological properties consisting of anti-inflammatory, anti-microbial, anti-oxidant, anti-cancer, and immunomodulatory activities. AIM: Therefore, we aimed to investigate the impacts of G. glabra on the development of post-operative abdominal adhesion in a rat model. METHODS: Male Wistar rats weighing 200-250 g were divided into six groups (n = 8): Group 1: normal group (non-surgical), and the surgical groups including Group 2: control group received the vehicle, Group 3: G. glabra 0.5% w/v, Group 4: G. glabra 1% w/v, Group 5: G. glabra 2% w/v, and Group 6: dexamethasone, 0.4% w/v. The intra-abdominal adhesion was performed utilizing soft sterilized sandpaper on one side of the cecum, and the peritoneum was slightly washed with 2 ml of the extract or vehicle. In addition, macroscopic examination of adhesion scoring and the levels of inflammatory mediators [interferon (IFN)-γ, prostaglandin E2 (PGE2)], fibrosis markers [interleukin (IL)-4, transforming growth factor (TGF)-ꞵ], and oxidative factors [malondialdehyde (MDA), nitric oxide metabolites (NO), and reduced glutathione (GSH)] were evaluated. In vitro toxicities were also done on mouse fibroblast L929 and NIH/3T3 cell lines. RESULTS: We found higher levels of adhesion (P < 0.001), IFN-γ(P < 0.001), PGE2(P < 0.001), IL-4(P < 0.001), TGF-ß(P < 0.001), MDA(P < 0.001), and NO(P < 0.001), and lower levels of GSH(P < 0.001) in the control group. In contrast, G. glabra concentration dependent and dexamethasone alleviated the levels of adhesion (P < 0.05), inflammatory mediators (P < 0.001-0.05), fibrosis (P < 0.001-0.05), and oxidative (P < 0.001-0.05) factors, while propagating the anti-oxidant marker (P < 0.001-0.05) in comparison to the control group. Results also showed that the extract did not significantly reduce cell viability up to 300 µg/ml (P > 0.05). CONCLUSION: G. glabra could concentration-dependently mitigate peritoneal adhesion formation through its anti-inflammatory, anti-fibrosis, and anti-oxidant properties. However, further clinical investigations are required to approve that G. glabra may be a promising candidate against post-surgical adhesive complications.

The possible mechanism of Datura stramonium on pentobarbital-induced sleep in mice.

BACKGROUND: Insomnia leads to the development of mental problems and missing of accuracy in affected persons. Various investigations have previously revealed which medicinal plants play a role in the improvement of insomnia. In this study, we evaluated the effect of hydro-alcoholic extract of Datura stramonium on insomnia in mice. METHODS: The extracts and fractions at different concentrations were injected intraperitoneally (i.p.) to mice 30 min before the sodium pentobarbital (30 mg/kg, i.p.). Additionally, the blood was collected from cardiac and serum separated to measure brain-derived neurotrophic factor (BDNF). The LC-MS was done to identify the active components. Flumazenil or naloxone were also applied to study the possible mechanism of extract. The PC12 cells were then exposed to different doses of extract and fractions, in order to evaluate cytotoxicity by MTT assay and the measured LD50. RESULTS: The hydro-alcoholic extracts of calyx, seed and petal elevated sleep duration and decreased sleep latency. In addition, water, ethyl acetate and n-butanol fractions of hydro-alcoholic extract of petal increased sleep duration. Of note, Naloxone significantly reversed the hypnotic effect of the extract. The extract increased the level of BDNF in serums. As well, the toxicity assessment revealed that the extracts had not toxic on PC12 cells. The LD50 value was obtained as 4.8 g/kg. CONCLUSION: This research demonstrated that D. stramonium (including seed, petal and calyx) increased the hypnotic effect without neurotoxicity on PC12 cells. Sleep induction may be related to its active ingredients as well as the effect on opioid receptors.

Effects of Capparis Spinosa extract on the neuropathic pain induced by chronic constriction injury in rats.

Neuropathic pain, a chronic pain condition, puts a considerable burden on its patients. However, different pathophysiological characteristics of neuropathic pain make the current treatment medications insufficient in controlling pain. Identifying treatment effects with Capparis Spinosa hydro-alcoholic extract in an animal model of neuropathic pain. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the components of C. Spinosa hydro-alcoholic extract. To establish a neuropathic pain model, adult male Wistar rats underwent chronic constriction injury (CCI) surgery in their left sciatic nerve. Male wistar rats were divided into four groups: CCI, Sham, CCI with C. Spinosa (100 mg/kg), and CCI with C. Spinosa (200 mg/kg). Rats were treated with a hydro-alcoholic extract from aerial parts of the C. Spinosa (orally, daily) starting from CCI induction until 14 days after. Behavioral tests (mechanical allodynia, cold allodynia, and thermal hyperalgesia) and biochemical tests (IL-1ß, TNF-α, MDA, and total thiol) were taken from animals. The LC-MS analysis identified 22 compounds in C. Spinosa extract with the predominance of flavonoids. CCI produced a significant (P < 0.001) increase allodynia (mechanical and cold) and thermal hyperalgesia in comparison with sham group. Oral administration of C. Spinosa significantly (P < 0.05) ameliorated CCI-induced nociceptive pain compared with CCI group. Spinal cord specimens of CCI rats had significant (P < 0.05) elevated inflammation status (↑IL-1ß, ↑TNF-α), and significant (P < 0.05) decreased antioxidative status (↑MDA, ↓total thiol) in comparison with the sham group. These changes were reversed following C. Spinosa treatment. C. Spinosa alleviates neuropathic pain by exhibiting antioxidative and anti-inflammatory effects. The responsible components for these effects are possibly the flavonoid compounds in C. Spinosa extract.

An evaluation of qH NMR: A complementary approach to GC-FID for quantification of Thymol and trans-Anethole in essential oils and supplements.

Sweet fennel (Foeniculum vulgare Mill. var. dulce) and thyme (Zataria multiflora Boiss.) are regarded as the important supplies for pharmaceutical, food, cosmetic, and perfume industries. The major components trans-anethole and thymol are represented in fennel and thyme, respectively. The essential oils (EOs) content and the value of their related constituents should be given in strict quality control due to the storage conditions, source, and adulterations. In this study, we compared the validation of quantitative 1H NMR (qH NMR) method with the gas chromatography with flame ionization detection (GC-FID) to quantify the trans-anethole and thymol in fennel and thyme EOs and their related supplements. The current results showed that the quantification of trans-anethole and thymol by qH NMR method was successfully achieved from their EOs and supplements. All the validation parameters including linearity, robustness, repeatability, and stability were authenticated for thymol and trans-anethole quantification. Similar results were obtained in both qH NMR and conventional GC-FID methods. Therefore, according to the measured values, the qH NMR method was adequate to determine the constituents of the EOs, with the results being roughly comparable to those obtained by GC-FID, with the advantage of being simple, repeatable, rapid (8-10 min, while for GC-FID 55 min) and essential for quality control of commercial samples.

Efficacy of Covexir® (Ferula foetida oleo-gum) treatment in symptomatic improvement of patients with mild to moderate COVID-19: A randomized, double-blind, placebo-controlled trial.

The SARS-CoV-2 COVID-19 pandemic has emerged as an unprecedented emergency state in healthcare system and global challenge. In recent decade, the function of exogenous H2 S in the treatment of respiratory diseases has been investigated using H2 S-donor agents. Ferula foetida is a medicinal plant that is traditionally used in respiratory diseases including asthma and viral respiratory diseases. The oleo-gum of this plant is a rich source of several organic sulfides including thiophenes, disulfides and polysulfide derivatives, which can act as H2 S-donor agents. The purpose of this study was to investigate the efficacy of Covexir® (F. foetida oleo-gum) treatment as a rich source of H2 S-donor compounds in clinical presentations of patients with COVID-19. The efficacy of Covexir® was evaluated in a randomized, double-blind, placebo-controlled trial in outpatients with COVID-19. Covexir® could significantly inhibit cough when compared to the placebo group (p < .01 and p < 001, respectively). Moreover, there was a significant difference (p < 001) between the two groups in dyspnea symptom at follow-up interval of 7 day after receiving Covexir®. Furthermore, on days 3 and 7, statistically significant differences were observed in myalgia, anorexia, anosmia, and sense of taste severity between two groups. Our findings revealed that Covexir® was very safe in the treatment of COVID-19 patients with mild to moderate symptoms and it can be recommended to improve clinical presentations of patients with COVID-19 such as cough, shortness of breath, myalgia, anorexia, anosmia, and sense of taste.

In silico exploration of disulfide derivatives of Ferula foetida oleo-gum (Covexir®) as promising therapeutics against SARS-CoV-2.

Although vaccines have been significantly successful against coronavirus, due to the high rate of the Omicron variant spread many researchers are trying to find efficient drugs against COVID-19. Herein, we conducted a computational study to investigate the binding mechanism of four potential inhibitors (including disulfide derivatives isolated from Ferula foetida) to SARS-CoV-2 main protease. Our findings revealed that the disulfides mainly interacted with HIS41, MET49, CYS145, HIS64, MET165, and GLN189 residues of SARS-CoV-2 main protease. The binding free energy decomposition results also showed that the van der Waals (vdW) energy plays the main role in the interaction of HIS41, MET49, CYS145, HIS64, MET165, and GLN189 residues with the inhibitors. Furthermore, it is found that the Z-isomer derivatives have a stronger interaction with SARS-CoV-2, and the strongest interaction belongs to the (Z)-1-(1-(methylthio)propyl)-2-(prop-1-enyl)disulfane (ΔG = -18.672 kcal/mol). The quantum mechanical calculations demonstrated that the second-order perturbation stabilization energy and the electron density values for MET49-ligand interactions are higher than the other residue-ligand complexes. This finding confirms the stronger interaction of this residue with the ligands.

Attenuation of isoprenaline-induced myocardial infarction by Rheum turkestanicum.

BACKGROUND: Oxidative stress plays a major role in the pathogenesis of myocardial infarction. This study evaluated the cardioprotective effects of the hydroalcoholic extract of Rheum turkestanicum on isoprenaline-induced myocardial infarction (MI) in Wistar rats. METHODS: In this study, we used liquid chromatography-mass spectrometry to determine the active compounds present in the extract. Thirty rats were divided to 5 groups (6 rats in each group). The extract was administered orally at the doses of 100 and 300 mg/kg body weight and then a subcutaneous injection of isoprenaline (85 mg/kg) was administered on the 8th and 9th days. Serum levels of lactate dehydrogenase (LDH), creatine kinase-MB (CK-MB), and creatinine kinase (CPK) were measured using standard commercial kits. Serum activities of superoxide dismutase, catalase, and cardiac levels of thiol and lipid peroxidation were also determined. Hematoxylin and eosin were used for histopathological staining. RESULTS: Phytochemical analysis revealed the presence of 24 compounds in the hydro-ethanolic extract of R. turkestanicum. Isoprenaline increased malondialdehyde (4.002 ± 0178, P < 0.001) while decreased thiol content (101.7 ± 6.186, P < 0.001). Moreover, reduced activities of superoxide dismutase (139 ± 10.88, P < 0.001) and catalase (2.812 ± 0.215, P < 0.001), and elevated levels of LDH (1245 ± 62.28, P < 0.001), CPK (898 ± 23.06, P < 0.001) and CK-MB (697 ± 50.22, P < 0.001) were observed. Pretreatment with the R. turkestanicum extract significantly reduced cardiac markers and increased thiol content as well as the activity of antioxidant enzymes. The extract attenuated the histopathological changes induced by isoprenaline. CONCLUSION: According to the obtained results, R. turkestanicum may be an appropriate candidate to reduce isoprenaline-induced MI through modulation of oxidative stress. Administration of the extract attenuated cardiac enzymes following isoprenaline administration. The cardioprotective action of the extract can be attributed to the bioactive antioxidant ingredients of R. turkestanicum. To identify the precise mechanisms, further investigations are required.

Cytotoxic sesquiterpene lactones and lignans from Cousinia turkmenorum Bornm (Asteraceae).

Seven sesquiterpene lactones, chlorophyssopifolin E (1), aguerin B (2), repdiolide triol (3), solistitiolide (4), aitchisonolide (5), sinicin B (6), cynaropicrin (7), along with four lignans arctigenin (8), arctiin (9), matairesinol (10), and matairesinoside (11) were isolated for the first time from the aerial parts of Cousinia turkmenorum Bornm. Among the isolated compounds, aguerin B (2) showed the most cytotoxic activity against MCF7 cell lines with IC50 value of 18.9 µM. Findings of this study could be useful for the development of new anticancer agents from nature.

Effect of Sanguisorba minor on scopolamine-induced memory loss in rat: involvement of oxidative stress and acetylcholinesterase.

Sanguisorba minor (S. minor) has neuroprotective and antioxidant activities. However, its potential benefits in ameliorating learning and memory functions have been explored in no studies up to now. So, in the current study, rats were treated with S. minor hydro-ethanolic extract (50, 100, and 200 mg/kg, intraperitoneal (i.p.)) as well as rivastigmine (0.5 mg/kg, i.p.) for 21 consecutive days. Thereafter, their behavioral performance was assessed using Morris water maze (MWM) and passive avoidance (PA) tasks. Notably, 30 min before conducting the tasks, scopolamine was injected. Finally, the biochemical assessments were done using the brain tissue. The extract characterization was performed by liquid chromatography-mass spectrometry, which confirmed the presence of quercetin, myricetin, kaempferol, catechin, ellagic acid, and gallic acid derivatives. In the MWM test, the extract reduced both escape latency and the travelled distance, compared to the scopolamine group. Moreover, in the PA test, the latency to enter the dark chamber significantly increased by the extract, compared to the scopolamine group (p < 0.05-p < 0.001). Notably, the beneficial effects of S. minor on cognitive performance of the scopolamine-treated rats appeared to be similar or even better than rivastigmine in behavior performance. Similar to rivastigmine, it was observed that the extract attenuated both AChE activity and oxidative injury in the brain as evidenced by the increased antioxidant enzymes and total thiol content; however, it decreased malondialdehyde level (p < 0.05-p < 0.001). In conclusion, the results suggested the effectiveness of S. minor in preventing cognitive dysfunction induced by scopolamine. Accordingly, these protective effects might be produced by the regulation of cholinergic activity and oxidative stress. S. minor could be considered as a potential alternative therapy in cognition disorders.

A mechanistic insight into the biological activities of urolithins as gut microbial metabolites of ellagitannins.

Urolithins are the gut metabolites produced from ellagitannin-rich foods such as pomegranates, tea, walnuts, as well as strawberries, raspberries, blackberries, and cloudberries. Urolithins are of growing interest due to their various biological activities including cardiovascular protection, anti-inflammatory activity, anticancer properties, antidiabetic activity, and antiaging properties. Several studies mostly based on in vitro and in vivo experiments have investigated the potential mechanisms of urolithins which support the beneficial effects of urolithins in the treatment of several diseases such as Alzheimer's disease, type 2 diabetes mellitus, liver disease, cardiovascular disease, and various cancers. It is now obvious that urolithins can involve several cellular mechanisms including inhibition of MDM2-p53 interaction, modulation of mitogen-activated protein kinase pathway, and suppressing nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Antiaging activity is the most appealing and probably the most important property of urolithin A that has been investigated in depth in recent studies, owing to its unique effects on activation of mitophagy and mitochondrial biogenesis. A recent clinical trial showed that urolithin A is safe up to 2,500 mg/day and can improve mitochondrial biomarkers in elderly patients. Regarding the importance of mitochondria in the pathophysiology of many diseases, urolithins merit further research especially in clinical trials to unravel more aspects of their clinical significance. Besides the nutritional value of urolithins, recent studies proved that urolithins can be used as pharmacological agents to prevent or cure several diseases. Here, we comprehensively review the potential role of urolithins as new therapeutic agents with a special focus on the molecular pathways that have been involved in their biological effects. The pharmacokinetics of urolithins is also included.

Antibacterial, Antioxidant and Melanogenesis Inhibitory Activity of Auraptene, a Coumarin from Ferula szowitsiana Root.

The auraptene is a geranyloxyn coumarin found in the Ferula species. The plant is endemic in Central Asia and it is used as a medicinal food in Iran. This research aimed to evaluate the antibacterial, antioxidant, and anti-melanogenic properties of auraptene, a coumarin from Ferula szowitsiana root. The results revealed that auraptene possessed antibacterial activity with minimum inhibitory and minimum bactericidal concentrations ranged from 2.5 up to 10 mg/ml against human pathogenic bacteria (Escherichia coli, Salmonella typhimurium, Salmonella paratyphi, Clostridium perfringens, Staphylococcus aureus). The nitric oxide scavenging activity (IC50: 670.9 µg/ml) showed its moderate antioxidant potential. Similarly, the results of ferric thiocyanate and thiobarbituric acid assays reconfirmed the moderate antioxidant activity of auraptene and indicated the percentage inhibitions of hydroxyl radicals to be 31.87 and 14%, respectively. The cell-based antioxidant evaluation confirmed the antioxidant activity of auraptene through up-regulation of the antioxidant-related genes including superoxide dismutase, catalase, and glutathione peroxidase in the human foreskin fibroblast (HFF). The auraptene has also displayed the anti-melanogenic activity through direct tyrosinase enzyme inhibition (IC50 of 29.7 µg/ml) and could modulate the expression of major melanogenesis-related genes including tyrosinase, tyrosinase-related protein 1, and dopachrome tautomerase in the murine melanoma cell line. The auraptene from Ferula szowitsiana root exhibited antibacterial, antioxidant, and melanogenesis inhibitory activities.

A Review of the Phytochemistry and Antimicrobial Properties of Origanum vulgare L. and Subspecies.

Origanum vulgare L. (O. vulgare) is an important medicinal herb of the family Lamiaceae. In the current study, we explained the critical evaluation of traditional uses, the phytochemistry and the antimicrobial properties of O. vulgare and its subspecies, with a focus on the mechanisms of actions of the most important phytochemicals from O. vulgare subspecies. The most important phytochemicals of O. vulgare are volatile (essential oil) and non-volatile phenolic compounds (phenolic acids & flavonoids). The constituents of the O. vulgare essential oil (EO) include high percentages of thymol and carvacrol with excellent antimicrobial activity alone or in combination with other antibiotics. Interesting results have been reported the remarkable antimicrobial activities of infusion or tea products of O. vulgare with a high amount of EO against multidrug-resistant bacterial and fungal microorganism (such as Escherichia coli, Staphylococcus aureus, Candida albicans and Pseudomonas aeruginosa). The most important antibacterial mechanisms of O. vulgare are enzyme inhibition, efflux pump inhibition, ATP depletion, biofilm formation inhibition and cytoplasmic membrane damage. The antimicrobial activity of the hirtum subspecies has been confirmed in different in-vitro and in-vivo studies. The present review confirms the clinical and preclinical research showing the O. vulgare and its subspecies antimicrobial effects.

Perspective on the application of medicinal plants and natural products in wound healing: A mechanistic review.

Wound is defined as any injury to the body such as damage to the epidermis of the skin and disturbance to its normal anatomy and function. Since ancient times, the importance of wound healing has been recognized, and many efforts have been made to develop novel wound dressings made of the best material for rapid and effective wound healing. Medicinal plants play a great role in the wound healing process. In recent decades, many studies have focused on the development of novel wound dressings that incorporate medicinal plant extracts or their purified active compounds, which are potential alternatives to conventional wound dressings. Several studies have also investigated the mechanism of action of various herbal medicines in wound healing process. This paper attempts to highlight and review the mechanistic perspective of wound healing mediated by plant-based natural products. The findings showed that herbal medicines act through multiple mechanisms and are involved in various stages of wound healing. Some herbal medicines increase the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-ß (TGF-ß) which play important role in stimulation of re-epithelialization, angiogenesis, formation of granulation tissue, and collagen fiber deposition. Some other wound dressing containing herbal medicines act as inhibitor of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and inducible nitric oxide synthase (iNOS) protein expression thereby inducing antioxidant and anti-inflammatory properties in various phases of the wound healing process. Besides the growing public interest in traditional and alternative medicine, the use of herbal medicine and natural products for wound healing has many advantages over conventional medicines, including greater effectiveness due to diverse mechanisms of action, antibacterial activity, and safety in long-term wound dressing usage.

Evaluation of the Therapeutic Effects of the Hydroethanolic Extract of Portulaca oleracea on Surgical-Induced Peritoneal Adhesion.

OBJECTIVE: Peritoneal adhesion (PA) is an abnormal connective tissue that usually occurs between tissues adjacent to damaged organs during processes such as surgery. In this study, the anti-inflammatory and antioxidant effects of Portulaca oleracea (PO) were investigated against postoperative-induced peritoneal adhesion. METHODS: Thirty healthy male Wistar rats (220 ± 20 g, 6-8 weeks) were randomly divided into four groups: (1) normal, (2) control (induced peritoneal adhesion), and (3) and (4) PO extracts (induced peritoneal adhesion and received 100 or 300 mg/kg/day of PO extract for seven days). Finally, macroscopic and microscopic examinations were performed using different scoring systems and immunoassays in the peritoneal lavage fluid. RESULTS: We found that the levels of adhesion scores and interleukin- (IL-) 1ß, IL-6, IL-10, tumour necrosis factor- (TNF-) α, transforming growth factor- (TGF-) ß 1, vascular endothelial growth factor (VEGF), and malondialdehyde (MDA) were increased in the control group. However, PO extract (100 and 300 mg/kg) notably reduced inflammatory (IL-1ß, IL-6, and TNF-α), fibrosis (TGF-ß 1), angiogenesis (VEGF), and oxidative (MDA) factors, while increased anti-inflammatory cytokine IL-10, antioxidant factor glutathione (GSH), compared to the control group. CONCLUSION: Oral administration of PO improved postoperational-induced PA by alleviating the oxidative factors, fibrosis, inflammatory cytokines, angiogenesis biomarkers, and stimulating antioxidative factors. Hence, PO can be considered a potential herbal medicine to manage postoperative PA. However, further clinical studies are required to approve the effectiveness of PO.

Comparative evaluation of the protective effects of oral administration of auraptene and umbelliprenin against CFA-induced chronic inflammation with polyarthritis in rats.

This study aimed to evaluate the anti-inflammatory effect of Auraptene (AUR) and Umbelliprenin (UMB) in a rat model of rheumatoid arthritis (RA) induced by using complete Freund's adjuvant (CFA). Paw swelling of adjuvant arthritis rats measured at various times after CFA injection. Over 15 days of RA induction, mediator/cytokine-mediated processes involved in managing the regulation and resolving RA's inflammation were also quantified with ELISA. Histopathological changes were also assessed under a microscope 15 days after the CFA injection. AUR at all doses and UMB administration only at a 16 mM /kg administration dose significantly reduced CFA-induced paw edema level compared to the control group. UMB (64 and 32 mM) and AUR (64, 32, and 16 mM) could reduce the PGE2 (p < .0001-.01) and NO (p < .0001-.05) levels in the treatment groups compared to the negative control group. However, these compounds showed no significant effect on the TNF-α, IFN-γ, TGF-ß, IL-4, and IL-10 levels than the control group (p > .05). Unlike indomethacin and prednisolone, treatment of rats with AUR (16, 32, and 64 mM/kg) and UMB (16 and 32 mM/kg) reduced the level of IL-2 (p < .0001). In all treatment groups, the serum level of IL-17 was significantly reduced compared to the CFA group (p < .001-0.05). We suggested AUR and UMB could diminish inflammation by reducing the serum level of IL-17 and could be considered a proper alternative in the treatment of IL-17 related inflammatory diseases such as rheumatoid arthritis. Given that AUR and UMB apply their anti-inflammatory effects by changing distinct cytokine release/inhibition patterns, their potential application in diverse inflammatory diseases seems different.