Effects of Komouni Formulation (Herbal Product of Persian Medicine) With a Low-Calorie Diet on Cardiometabolic Risk Factors in Overweight and Obese Women: A Triple-Blinded Randomized Clinical Trial.

Background: The prevalence of obesity has almost tripled since 1975, and obesity places a heavy economic burden on healthcare systems. There is a high tendency to use a variety of complementary medicine modalities for weight management among obese patients. Persian Medicine is an ancient medical school practiced for thousands of years in Iran. Found in reliable Iranian traditional resources, Komouni formulation (KF) is a compound medicine that can be effective in the treatment of obesity. It comprises black caraway (Bunium persicum Boiss.), anise (Pimpinella anisum L.), fennel (Foeniculum vulgare Miller), and ajwain (Trachyspemum ammi L.). Objectives: This study aimed to determine the effects of KF on anthropometric indices and metabolic parameters in overweight and obese women. Methods: This triple-blinded randomized controlled clinical trial was performed on 70 overweight or obese women aged 20 - 40 years, with a body mass index (BMI) of 25 - 34.9 kg/m2. The subjects were randomly divided into two groups (each group n = 35) to receive a calorie-restricted diet with 2 g/day (500 mg 30 minutes before breakfast, 1000 mg 30 minutes before lunch, and 500 mg 30 minutes before dinner) KF or placebo for 8 weeks. Anthropometric indices, food intake, and biochemical parameters were measured at baseline and after the intervention. Results: A total of 60 women (intervention = 30; placebo = 30) completed the trial. After the intervention, the KF group experienced a significant reduction in weight (-4.8 vs. -3.2 kg; P = 0.0001), BMI (-1.8 vs. -0.79 kg/m2; P = 0.0001), waist circumference (-5.28 vs. -3.20 cm; P = 0.004), hip circumference (-0.018 vs. -0.008 cm; P = 0.047), fasting blood sugar (-5.6 vs. 0.33; P = 0.025), and low-density lipoprotein (-11.7 vs. 6.7; P = 0.0001), compared to the placebo group. None of the patients in the intervention and placebo groups reported any side effects. Conclusions: Using KF, along with a calorie-restricted diet, can reduce cardiometabolic risk factors in overweight and obese women. However, further studies are needed to elucidate the efficacy of KF as a complementary therapy in obesity.

Early historical report of alcohol hepatotoxicity in Minooye Kherad, a Pahlavi manuscript in Ancient Persia, 6th century CE.

Background: Historical evidence revealed that alcoholic beverages have been produced, used and abused thousands of years before the discovery of alcohol by Rhazes for medical purposes. Alcohol-induced liver disease (e.g., steatosis, steatohepatitis, fibrosis and cirrhosis) is one of the most prevalent causes of chronic liver disease all over the world. This study aims to find the early report of this complication in an ancient Persian historical text. Methods: In this study, the book of Minooye Kherad, a Zoroastrian manuscript on wisdom which was written in the late Sassanid Empire (224-637 CE) is reviewed. Results: However, the concept of alcohol hepatotoxicity as one of the most important complications of alcoholism is a new terminology, by researching historical documents it can be found that one of the oldest reports of benefits and disadvantages of drinking wine focusing on liver complications is mentioned in the book of Minooye. Conclusion: Description of the liver disease and damage caused by excessive alcohol consumption in this valuable book can be considered as the early report of hepatotoxicity of alcoholic beverages in the medical history.

The effects of Silymarin on the features of cardiometabolic syndrome in adults: A systematic review and meta-analysis.

Some medicinal herbs and their effective components showed positive effects on the features of the cardiometabolic syndrome (CMS). The aim of the present systematic review and meta-analysis is to examine the effects of silymarin on the components of CMS in adults. Four electronic databases including PubMed/Medline, Scopus, Web of Science, and Embase were systematically searched up to December 31, 2020 to identify all eligible clinical trials. A random-effect model using DerSimonian and Laird method was used to estimate the pooled weighted mean differences (WMDs) and the 95% confidence intervals (95%CIs). Finally, 11 clinical trials met the eligibility criteria. Our results demonstrated that silymarin significantly reduced the levels of fasting blood glucose (WMD: -17.96 mg/dL, 95% CI: -32.91, -3.02;I2 : 82.4%, p < 0.001), hemoglobin A1C (WMD: -1.25%, 95% CI: -2.34, 0.16; I2 : 92.9%, p Ë‚ 0.001), total cholesterol (WMD: -17.46 mg/dL, 95% CI: -30.98, -3.95; I2  = 62.9%, p = 0.006), triglyceride (WMD: -25.70 mg/dL, 95% CI: -47.23, -4.17; I2 :54.3%, p = 0.025), low-density lipoprotein-cholesterol (WMD: -10.53, 95% CI: -19.12, -1.94; I2: 37.5%, p = 0.119) and increased high-density lipoprotein- cholesterol (WMD: 3.36 mg/dL, 95% CI: 0.88, 5.84; I2 : 37.4%, p = 0.120) compared to placebo. However, its effects on BMI were not statistically significant. Silymarin can be an effective complementary therapy to improve most features of CMS. However, due to high heterogeneity and limited clinical trials in some parameters, further high-quality clinical trials are needed to confirm its efficacy.

COVID-19: General Strategies for Herbal Therapies.

The coronavirus disease-2019 (COVID-19) pandemic started in early 2020 with the outbreak of a highly pathogenic human coronavirus. The world is facing a challenge and there is a pressing need for efficient drugs. Plants and natural compounds are a proven rich resource for new drug discovery. Considering the potential of natural products to manage the pandemic, this article was designed to provide an inclusive map of the stages and pathogenetic mechanisms for effective natural products on COVID-19. New drug discovery for the COVID-19 pandemic can encompass both prevention and disease management strategies. Preventive mechanisms that may be considered include boosting the immune response and hand hygiene in the preexposure phase; and blocking of virus binding and entry in the postexposure phase. Potential therapeutic target mechanisms include virus-directed therapies and host-directed therapies. Several medicinal plants and natural products, such as Withania somnifera (L.) Dunal and propolis for prevention; Tanacetum parthenium (L.) for treatment; and Ammoides verticillata (Desf.) Briq and Nigella sativa L. for both prevention and treatment have been found effective and are good targets for future research. The examples of phytochemical compounds that may be effective include aloin and terpenes as anti-septics; isothymol, dithymoquinone, and glycyrrhizin as inhibitors of virus binding and entry; glycyrrhizin, and berberine as replication suppressants; ginsenoside Rg1 and parthenolide as immunomodulators; and eriocitrin, rhoifolin, hesperidin, naringin, rutin, and veronicastroside as anti-complements. Recognizing different mechanisms of fighting against this virus can lead to a more systematic approach in finding natural products and medicinal plants for COVID-19 prevention and treatment.

Efficacy of Persian medicine herbal formulations (capsules and decoction) compared to standard care in patients with COVID-19, a multicenter open-labeled, randomized, controlled clinical trial.

Persian medicine has recommended clinical experiences and proper herbal remedies for prevention and treatment of microbial infections and respiratory diseases. An open-label, randomized, controlled, multicenter trial was conducted at five hospitals in Tehran and Isfahan provinces of Iran on 358 hospitalized adult patients. A total of 174 patients received standard care and 184 received herbal remedies (polyherbal decoction every 8 hr and two herbal capsules every 12 hr) plus standard care for 7 days. The primary clinical endpoint was the duration of hospital stay, and secondary outcomes were clinical improvement of symptoms based on self-assessment questionnaire. Results demonstrated that these natural decoction and capsules treatment plus routine care significantly decreased duration of hospital dyspnea (3.291 day vs. 6.468 days), accelerated clinical improvement, and decreased symptoms such as dry cough, dyspnea, muscle pain, headache, fatigue, anorexia, chills, runny nose, sputum cough, and vertigo in the treatment group compared with standard-care group. Significant effects of these polyherbal formulations on improving the symptoms of COVID-19 could be incredibly promising for managing this pandemic with acceptable tolerability.

The Early Report of Herpetic Whitlow by Bahal-Dawlah Razi in 15th Century CE.

A herpetic whitlow is a lesion (whitlow) on a finger or thumb caused by herpes simplex virus. It is a painful infection that typically affects the fingers or thumbs. Occasionally infection occurs on the toes or on the nail cuticle. Symptoms of herpetic whitlow include tenderness, swelling and reddening of the infected finger skin, fever and swollen lymph nodes. Although, it is believed that the first recorded observations were in 1909 CE by H. G. Adamson, in the medieval period, Bah?' al-Dawlah N?rbakhsh? Razi (1501 CE) described herpetic whitlow, under the title of Dakhes in Khulasat al-Tajarib (The Summary of Experience), his book on medicine. Some of Baha al-Dawlah's descriptions and his etiology of Dakhes are based on humoral theories and cannot be concurred with current medical concepts, but more symptoms and clinical manifestations are consistent with current definitions. It seems the earliest description of herpetic whitlow in the medical history.

The effect of a hydrogel made by Nigella sativa L. on acne vulgaris: A randomized double-blind clinical trial.

Nigella sativa L. (black seed) is one of the main medicinal plants frequently cited in traditional Persian medicine manuscripts for management of acne vulgaris. The present study was designed to investigate the efficacy of a topical preparation from N. sativa in acne vulgaris. In a randomized double-blind controlled clinical trial, 60 patients (30 patients in treatment and 30 in placebo group) were randomly received N. sativa hydrogel (standardized based on thymoquinone) or placebo hydrogel, twice daily for 60 days. The Investigator's Global Assessment (IGA) grading score was recorded for each patient. Moreover, acne disability index (ADI) was evaluated using a standard questionnaire filled out by the patients at the beginning and end of the study. A 78% mean reduction in the IGA score on the N. sativa-treated group was recorded compared with 3.3% on the vehicle-treated one. Significant reductions in the number of comedones, papules, and pustules were observed in the treatment group compared with placebo after 2 months. Also, ADI was decreased 63.49% in the treatment versus 4.5% in the placebo groups. No adverse event was recorded. N. sativa hydrogel had significant effects on improving the symptoms of acne vulgaris with acceptable tolerability.

Promising plant-derived secondary metabolites for treatment of acne vulgaris: a mechanistic review.

Acne vulgaris is the most common skin condition associated with inflammation of pilosebaceous unit. Since conventional therapies have not demonstrated desirable effectiveness and possess remarkable side effects, there is a growing interest in the use of herbal medicines for the management of acne vulgaris. In this study, plant-derived molecules investigated in acne vulgaris have been reviewed and their possible underlying mechanisms of action were discussed. For this purpose, different electronic databases including PubMed, Scopus, Cochrane library and Google Scholar were searched to obtain any in vitro, in vivo, or human studies evaluating the phytochemicals in the management of acne vulgaris. Data were collected from 1980 to 2018 (up to October). Most of the phytochemicals investigated in acne were from the category of polyphenols including resveratrol, myricitrin, schisandrin, terchebulin, alpha-mangotin, curcumin, ellagic acid and epigallocatechin 3-gallate. Moreover, alkaloids and terpenoids such as berberine, ursolic acid, lupeol were evaluated in acne vulgaris with less abundance. Various molecular mechanisms were involved in effects of phytochemicals including antioxidant (through down-regulation of H2O2, MDA, ROS and upregulation of SOD), anti-inflammatory (through reduction of proinflammatory cytokines, i.e., IL-1ß, IL-6, IL-8, TGF-ß, TNF-α, NF-κB), immunomodulatory, antibacterial (against Propionibacterium acnes and Propionibacterium granulosum), antiandrogenic, reducing sebum production, and lipogenesis inhibitory activities. Therefore, phytochemicals seem to be a precious source for identifying new medicines for treatment of acne vulgaris; however, since most of studies are preclinical, further clinical studies are needed to achieve more conclusive and reliable results.

Implications of grape extract and its nanoformulated bioactive agent resveratrol against skin disorders.

The grape seed extract (GSE) and its main active polyphenol, resveratrol (RES), have shown considerable antioxidant activities, besides possessed protective and therapeutic effects against various skin complications. This paper discusses the favorable effects of RES, GSE and their nanoformulations for dermatological approaches, with specific emphasis on clinical interventions. In this manner, electronic databases including PubMed, Science Direct and Google Scholar were searched. Data were collected from 1980 up to February 2019. The search terms included "Vitis vinifera", "grape", "resveratrol", "skin", "dermatology", and "nanoformulation". To increase the skin permeability of GSE and RES, several innovative nanoformulation such as liposomes, niosomes, solid-lipid nanoparticles, nanostructured lipid carriers, and lipid-core nanocapsule has been evaluated. According to our extensive searches, both RES and GSE have beneficial impacts on skin disorders such as chloasma, acne vulgaris, skin aging, as well as wound and facial redness. More clinical studies with nanoformulation approaches are recommended to achieve conclusive outcomes regarding the efficacy of RES and GSE in the management of skin diseases.

Plant-derived medicines for treatment of endometriosis: A comprehensive review of molecular mechanisms.

Endometriosis is an estrogen-dependent disease with inflammatory lesions at extra-uterine sites, causing pelvic pain and fertility reduction. Conventional therapies primarily focus on reducing systemic levels of estrogens; however, they do not have desirable effectiveness and possess considerable side effects. Therefore, there is a growing interest in the use of herbal medicine for the treatment of endometriosis. In this paper, electronic databases including PubMed, Scopus, Cochrane library and Google Scholar were searched to obtain any studies evaluating any herbal products in the management of endometriosis. Data were collected from 1980 to 2018. Most of studies investigating the effect of herbal medicines in endometriosis were in vitro and animal and only three clinical trials were found; one on Pinus pinaster bark extract (Pycnogenol) and two on Chinese herbal formulas. The studies on phytochemicals had mostly focused on polyphenolic compounds (epigallocatechin-3-gallate, genistein) and sesquiterpenes (ß-caryophyllene, parthenolide). Various molecular mechanisms of action have been involved in beneficial effects of herbal medicines and phytochemicals including anti-inflammatory (via reduction of proinflammatory cytokines such as interleukin -1, interleukin -6, interleukin -8, transforming growth factor-beta, tumor necrosis factor-α, nuclear factor-kappa B, growth factors, monocyte chemoattractant protein-1), antioxidant (through downregulation of hydrogen peroxide, malondialdehyde, reactive oxygen species and upregulation of superoxide dismutase), anti-proliferative and apoptotic (via enhancing Bcl-2-associated X protein/ B-cell lymphoma-2 and caspase3, 8 and 9 activity), anti-angiogenic (by downregulation of vascular endothelial growth factor receptors/ vascular endothelial growth factor), anti-invasive (via decreasing expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and matrix metalloproteinases), immunomodulatory, and estrogen modulating activities. So, medicinal plants seem to be a valuable source for identifying new drugs for treatment of endometriosis; however, since most of studies are preclinical, further clinical trials are required to achieve more conclusive results.

A Historical Report on Preparing Sustained Release Dosage Forms for Addicts in Medieval Persia, 16th Century AD.

For several centuries, opium addiction has been a social problem all over the world. It has been prevalent in Iran from the Safavid era (1501-1736 A.D). During this period, Hakim Imad al-Din Mahmud ibn-Mas'ud Shirazi (1515-1592 A.D), also known as Imad was one of the Persian physicians who wrote one of the earliest books in the field of opium and addiction (called Afiounieh) in history. In this book, he introduced two sustained release rectal (suppository) and oral (pill) dosage forms for Muslim addicts who fast in the month of Ramadan. He aimed to formulate them for these people so that they could keep fasting by using the slow release drugs. In these formulations, his innovation has important impacts in the history of both addiction and pharmaceutical sciences.

Clinical risks of St John's Wort (Hypericum perforatum) co-administration.

INTRODUCTION: St. John's wort (SJW) is a common medicinal herb used for the treatment of mild to moderate depression. Hyperforin, one of the chief components of SJW, plays an important role in the induction of cytochrome P450 enzymes (CYP) and P-glycoprotein transporter (P-gp), and therefore, affects the pharmacokinetics of various drugs. There are several clinical studies demonstrating the interaction of SJW with the metabolism of conventional drugs which may cause life-threatening events. Areas covered: This review focuses on human studies that have evaluated pharmacokinetic alterations of conventional drugs in concomitant use with different SJW preparations. Expert opinion: SJW preparations have demonstrated clinically important interactions with several classes of conventional drugs such as immunosuppressants, anticancer agents, cardiovascular drugs, oral contraceptives, and lipid lowering agents that caused life-threatening events in several cases. The patient information label on the SJW products should provide enough information regarding the possible risk of interaction. Hyperforin seems to be the major ingredient responsible for CYP and P-gp inducing activity of SJW; thus, hyperforin-free products may be future candidates to decrease SJW's drug interactions.

A Comparative Study of Allium Hirtifolium in Traditional and Modern Medicine.

BACKGROUND: Shallots (wild garlic/Osghordion) with the scientific name of Allium hertifolium, is one of the most famous plants from the Alliaceae family. For a long time, shallots have been used as a source of food and medicine in Iran. The active ingredients of the plant could be referred to agapentagenin, allicin, omega-3, omega-6, and minerals such as potassium, sodium, magnesium, iron, copper, zinc, and manganese. This study was conducted to compare shallots in the traditional and modern medicine in order to make a better use of this precious plant. METHODS: To collect appropriate data, resources and articles in trustworthy databases (e.g. Cochrane library, PubMed, Google Scholar) and traditional literature (e.g. Makhzan-ul-Adwiah, Canon, Zakhireh-ye Khwarazmshahi) were studied. Subsequently, the findings were reviewed, classified, and reported in a tabular format. RESULTS: Shallots are rich in fatty acids and minerals with many pharmacological effects such as its effect on the respiratory and nervous system and blood dilution, as reflected in the modern medicine. However, certain effects as mentioned in traditional medicine (e.g. anti-warts, anti-lipoma, anti-kidney stone, and its diuretic effects) are not covered in research studies of the modern medicine. CONCLUSION: Depending on its natural habitats, shallots have different pharmacological effects for which many usages are mentioned in traditional medicine. Some of these effects have been investigated in modern medicine; however, further evaluation of its safety and dosages for clinical use is necessary. Furthermore, some cases have not been studied in modern medicine, which could be the basis for future research.

Effect of donor tumor necrosis factor-alpha and interleukin-10 genotypes on delayed graft function and acute rejection in kidney transplantation.

INTRODUCTION: This study evaluated the influence of interleukin-10 (IL10) gene -1082G>A and tumor necrosis factor-alpha (TNF) gene -308G>A polymorphisms in the donor and recipients on the acute rejection (AR) episodes and delayed graft function (DGF) in kidney transplant recipients. MATERIALS AND METHODS: The IL10 -1082G>A and TNF -308G>A polymorphisms were determined in 100 kidney allograft recipients and their donors using the polymerase chain reaction-amplification refractory mutation system polymerase chain reaction-restriction fragment length polymorphism methods. Transplantation outcomes were determined in terms of AR and DGF criteria. RESULTS: The A allele of the TNF polymorphism (high producer) in the donors was associated with DGF in the recipients (odd ratio, 3.1; 95% confidence interval, 1.2 to 8.1). There was also a significant association between the combination of donor's IL10-TNF genotypes and DGF (odd ratio, 4.8; 95% confidence interval, 1.4 to 17.1); the frequency of a combination of IL10 AA or GA and TNF AA or GA was higher in the recipients with DGF. No association was found between the donors and recipients' IL10 -1082G>A and TNF -308G>A polymorphisms and AR. No association was detected between recipients and donors' IL10 polymorphisms or recipients' TNF polymorphisms and DGF. CONCLUSIONS: This study showed that donors with high TNF production may have increased risk of DGF in their recipients. Routine screening of these gene polymorphisms may have a clinical role in identifying patients at risk of DGF.

Chemokine receptor 2-V64I and chemokine receptor 5-Delta32 polymorphisms and clinical risk factors of delayed graft function and acute rejection in kidney transplantation.

INTRODUCTION: Chemokines and chemokine receptors have a pivotal role in immunity and inflammation. We aimed to evaluate their role in kidney transplant rejection. MATERIALS AND METHODS: The association of chemokine (C-C motif) receptor 2 (CCR2)-V64I and CCR5-Delta32 gene polymorphisms with acute rejection (AR) and delayed graft function (DGF) were examined in 100 donor-recipient pairs. The CCR2-V64I and CCR5-Delta32 alleles were determined using polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism, respectively. RESULTS: No associations were found between donors or recipients' CCR2-V64I and CCR5-Delta32 gene polymorphisms and AR or DGF. Of the characteristics of the donors, recipients, and transplantation, glomerulonephritis as a cause of kidney failure in the recipients was weakly associated with AR (relative risk, 6.1; 95% confidence interval, 0.8 to 46.0; P = .07). Transplantation of kidney from females to males was weakly associated with DGF (relative risk, 5.5; 95% confidence interval, 0.9 to 33.0; P = .06). There was a significant association between AR, but not DGF, and graft loss in the patients (relative risk, 28.6; 95% confidence interval, 1.7 to 487.0; P = .03). CONCLUSIONS: Our study failed to suggest CCR2-V64I or CCR5-Delta32 gene polymorphisms as risk factors for AR and DGF in kidney transplantation. Sex-matching between donors and recipients should be considered for living donor kidney transplantation.