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Introduction: According to Rome IV, functional dyspepsia is diagnosed with the presence of dyspepsia in the absence of organic or metabolic causes. FD caused by several factors, such as impaired gastric accommodation and hypersensitivity to gastric distention. Several studies have reported the effectiveness of herbal medicine on FD. This article, thus, reviews Persian herbal medicine in FD. Methods: Electronic databases, including Pubmed, Scopus, Cochrane, Embase, Web of science and Ovid, were searched so as to find clinical articles related to dyspepsia and herbal medicine by July 2019. Our search strategies were traditional medicine, complementary and alternative medicine, herb, plant, and dyspepsia. We excluded all articles except Persian clinical trials. Results: We found 34 clinical trials with 15 herbs and 4 compound herbal remedies like Asparagus racemosus, Brassica oleracea, Cynara scolymus, Ocimum basilicum, Mentha longifolia, Mentha pulegium, Mentha piperata, Pimpinella anisum, Nigella sativa, Mastic gum, Curcuma longa, Pistatio Atlantica, Glycyrrhiza glabra, Solanum tuberosum and Zingiber officinale and compound remedies of Rosa damascene & Crocus sativus, Trachyspermum copticom & Apium graveolence, Carum carvi & Mentha pipperata, Gingiber officinalis & Cynara scolymus are effective in functional dyspepsia. Conclusion: Many people use herbal and traditional remedies for the treatment of disorders such as gastrointestinal disorders, especially in Asian countries. Several studies reported the efficacy of herbal medicine in functional dyspepsia. Although their mechanisms are not fully understood, it seems they can modulate GI motility and improve symptoms of FD.

Osteoarthritis (OA) is known to be the leading cause of pain and disability in the elderly. The prevalence of this disease in adults over 60 years was 9.6% in men and 18% in women. The therapeutic goals of this disease generally include pain relief with the least side effects, improvement of articular function and improvement of life, in which pharmacological and nonpharmacological treatments are performed in different protocols. Due to the common side effects of pain relievers and complaints after invasive joint surgeries, there is a growing interest in the use of Traditional and Complementary protocols in OA treatment. In this paper, different sources of Traditional Persian Medicine (TPM) were searched to obtain any evidence evaluating any medicinal plants in the management of OA. Over 250 effective medicinal plants for the treatment of OA have been introduced in these sources, and by searching electronic databases including PubMed and Scopus, we have found that of these plants, 39 have direct or indirect evidence in the treatment of this complication by different mechanism of actions such as effect on Body mass index (BMI), obesity and dyslipidemia, anti-inflammatory, anti-nociceptive and antioxidant activity. The most important medicinal plants with direct evidence in the management of OA are Allium sativum, Commiphora mukul, Linum usitatissimum, Matricaria chamomilla, Nigella sativa, Zingiber officinale, and Piper nigrum. Medicinal plants seem to be a valuable source for discovering and identifying new drugs for treatment of OA; however, since most of the studies are preclinical, further clinical trials are required to achieve more conclusive results.

Background: Cough is one of the most common medical symptoms for which medical advice is sought. Although cough is a protective reflex responsible for clearing the airways from secretions and foreign bodies, it can be a troublesome symptom that causes discomfort to patients. Due to the increasing interest in herbal remedies in both developed and developing countries, in the current study, we aimed to overview medicinal herbs containing essential oils used as antitussive agents according to Traditional Persian Medicine (TPM) textbooks. We summarized the relevant scientific evidence on their possible pharmacological effects. Methods: To collect the evidence for the treatment of cough or “seaal” (cough in ancient books) from TPM sources, five main medicinal Persian manuscripts were studied. The antitussive herbs were listed and their scientific names were identified and authenticated following botanical reference books. ScienceDirect and PubMed online databases were searched for related mechanisms of action of the reported medicinal plants. Results: Forty-nine herbs containing essential oils have been recommended in TPM for the treatment of cough; 21 of them had at least one known mechanism of action for cough suppression in the scientific literature. According to this review, most of the cited medicinal plants were assessed for either nitric oxide inhibitory or antitussive/expectorant activities. Conclusion: In addition to advantageous effects of antitussive herbs recommended by TPM, the present review highlighted some recent evidence-based data on these promising herbs that could be used as an outline for future research on their medicinal use.

Coronavirus disease 2019 (COVID-19) is a debilitating disease with numerous medical and non-medical consequences. Our study aimed to evaluate the efficacy of Persian barley water in controlling the clinical outcomes of hospitalized COVID-19 patients.This was a single-blind, add-on therapy, randomized controlled clinical trial conducted in Shiraz, Iran, from January to March 2021. One hundred hospitalized COVID-19 patients with moderate disease severity were randomly allocated to receive routine treatment (per local protocols) with or without 250 ml of Persian barley water (PBW) daily for two weeks. Clinical outcomes and blood tests were recorded before and after the study period. Multivariable modeling was applied using Stata software for data analysis.The PBW product passed our standardization and safety assessments. Length of hospital stay (LHS) was 4.5 days shorter in the intervention group than the control group regardless of history of cigarette smoking (95% confidence interval: -7.22, -1.79 days). Also, body temperature, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and creatinine significantly dropped in the intervention group compared to the control group. No adverse events related to PBW occurred.This clinical trial demonstrated the efficacy of PBW in minimizing the LHS, fever, and levels of ESR, CRP, and creatinine among hospitalized COVID-19 patients with moderate disease severity. More robust trials can help find safe and effective herbal formulations as treatments for COVID-19.

The goal of this study is to evaluate the chemical compounds, the anti-bacterial/fungal activity, and the cytotoxicity of the essential oil of three species of lamiaceae in Iran. After the extraction of the essential oil implementing the hydrodistillation method, the analysis and identification of the compounds were carried out with a chromatograph coupled with a mass spectrometer. For the evaluation of the anti-bacterial/fungal activity of the essential oils, the measurement of the diameter of inhibition halo, the minimum inhibitory concentration (MIC), bactericidal and fungicidal concentrations (MBC/MFC) were utilized; and for the evaluation of the cytotoxic activity of the essential oils, the 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) method was used. The results show that the dominant compounds in the Perovskia abrotanoides Kar essential oil were camphor (21.68%), 1,8-cineole (14.26%), and α-pinene (7.23%); moreover, the dominant compounds in the Salvia reuteriana Boiss. Essential oil were benzyl benzoate (27.10%), linalool (13.27%), and sclareol (7.75%); in addition, the dominant compounds in the Ziziphora clinopodioides subsp. rigida (Boiss.) Rech.f. were cyclofenchene (25.29%), pulegone (14.14%), and menthol (7.70%). The largest halo diameter of inhibition halo (~ 22 mm) was against Streptococcus pyogenes and the strongest inhibiting and killing activity was against Candida albicans (MIC and MFC = 125 μg/mL) shown by the S. reuteriana essential oil which, respectively, matched the control antibiotics rifampin and nystatin. The analysis of the MTT test results showed that the Z. clinopodioides subsp. rigida essential oil (with IC50 value of ~ 144.2500) had the strongest cytotoxic activity against human ovarian cancer cells (OVCAR-3). On the whole, the results show that the essential oil of the Lamiaceae family plants is a source for various compounds with potential biological activities which can serve as a possible alternative to produce herbal medicine which are effective on some microorganisms and cancer cell lines.

Objective Developing an ontology can help collecting and sharing information in traditional medicine including Persian medicine in a well-defined format. The present study aimed to develop an ontology for gastric dystemperament in the Persian medicine. Methods This was a mixed-methods study conducted in 2019. The first stage was related to providing an ontology requirements specification document. In the second stage, important terms, concepts, and their relationships were identified via literature review and expert panels. Then, the results derived from the second stage were refined and validated using the Delphi method in three rounds. Finally, in the fourth stage, the ontology was evaluated in terms of consistency and coherence. Results In this study, 241 concepts related to different types of gastric dystemperament, diagnostic criteria, and treatments in the Persian medicine were identified through literature review and expert panels, and 12 new concepts were suggested during the Delphi study. In total, after performing three rounds of the Delphi study, 233 concepts were identified. Finally, an ontology was developed with 71 classes, and the results of the evaluation study revealed that the ontology was consistent and coherent. Conclusion In this study, an ontology was created for gastric dystemperament in the Persian medicine. This ontology can be used for designing future systems, such as case-based reasoning and expert systems. Moreover, the use of other evaluation methods is suggested to construct a more complete and precise ontology.

Persian Medicine, which flourished in the Islamic Golden Age (9th to 12th century AD), considers the human body a unified whole whose organs are in constant interaction and equilibrium with each other. The skin is one of these interdependent organs that play an important role in protecting internal organs, and as an excretion route, it can expel substances that are not consumed by the body. Alternatively, the uterus, a vital organ in pregnancy, excretes excess body material during menstruation to maintain a woman’s health. This narrative study discussed the importance of aligning the structure and function of these two organs based on the main textbooks of Persian Medicine, especially those written during this historical period. Likewise, electronic databases were used for investigating related articles.The skin and uterus are two excretory organs. When the secretion of excess material through menstruation is physiologically or pathologically impaired, the body transfers these substances to the skin as the organ associated with the uterus. Thus, the clinical manifestations of some skin diseases can be a sign of imbalance in the function of the uterus and its related organs. Consequently, the structural and functional similarities of both organs can provide a new guide in the approach to their participatory diseases in the integration of Persian and conventional medicine., Perzijska medicina, koja je procvjetala u zlatnom dobu islama (od 9. do 12. stoljeća), smatra ljudsko tijelo jedinstvenom cjelinom čiji su organi u stalnoj interakciji i ravnoteži jedni s drugima. Koža je jedan od tih međusobno ovisnih organa koji imaju važnu ulogu u zaštiti unutarnjih organa te kao sustav za izlučivanje može izlučivati tvari koje tijelu nisu potrebne. Alternativno, maternica, vitalni organ u trudnoći, izlučuje višak tjelesnog materijala tijekom menstruacije kako bi održala zdravlje žene. Ova narativna studija govori o važnosti usklađivanja strukture i funkcije tih dvaju organa na temelju važnih udžbenika perzijske medicine, posebno onih napisanih tijekom ovoga povijesnog razdoblja. Jednako tako, elektroničke baze podataka korištene su za istraživanje članaka. Koža i maternica dva su organa za izlučivanje. Kada je izlučivanje viška tvari menstruacijom fiziološki ili patološki poremećeno, tijelo te tvari prenosi na kožu kao organ koji je povezan s maternicom. Dakle, kliničke manifestacije nekih kožnih bolesti mogu biti znak neravnoteže u funkciji maternice i srodnih organa. Posljedično, strukturne i funkcionalne sličnosti obaju organa mogu pružiti nov pogled u pristupu njihovim participativnim bolestima, uz integraciju perzijske i konvencionalne medicin

Background: Free radicals can lead to liver dysfunction. Quality control of traditional formulations ensures their safe, pure, and pharmaceutical efficacy. “Qurs-e-Vard”, containing petals of Rosa damascena Mill., fruits of Rhus coriaria L. and roots of Glycyrrhiza glabra L. has been suggested as a hepatoprotective preparation in Traditional Persian Medicine (TPM). Objective: This study was directed at the evaluation of the phytochemical characterization, standardization, and in vitro antioxidant activity determination of a solid formulation and its components. Method: Some qualitative and quantitative controls were performed like ash value, heavy metals investigation, and microbial contamination. The phytochemical assays were used for obtaining total phenolic and flavonoid contents with spectrophotometric methods. 2, 2-Diphenyl-1-c (DPPH) and Nitric Oxide (NO) assays were run for determining Radical scavenging activities of the formulation and its components. Ferric reducing antioxidant power assay (FRAP) was determined as well. Results: Total phenolic contents of hydroalcoholic and aqueous extracts of the polyherbal formulation measured respectively, (376±0.93) and (297.6±0.96) mg of gallic acid/g of dry matter. Total flavonoid contents of the formulation were also measured (36.27±0.98) for hydroalcoholic extract and (17.79±0.86) mg of quercetin/g of dry matter for aqueous extract. The IC50 of hydroalcoholic and aqueous extract was obtained (88.14±1.15) and (140.78±2.98) μg/ml, respectively. NO scavenging percentages (200μg/ml) of hydroalcoholic and aqueous extracts were measured (59.11±2.15) and (65.08±2.35). FRAP values of hydroalcoholic and aqueous extracts were achieved (255.24±3.45) and (134.57±3.45) μg/ml as well. Conclusion: Our findings indicated that this polyherbal formulation and its components have justifiable antioxidant effects.

Traditional medicine has a long history and plays an important role in the Kurdish community in Sarvabad county, Kurdistan province, Iran. Despite the great diversity of medicinal plants, cultural history, and variety of herbal medicine uses among Kurdish tribes, very few cohesive ethnopharmacological studies of this unique region are available in the scientific literature. Our study tried to gather medicinal plant species and document the associated indigenous knowledge of the ethnic groups in the Sarvabad district for the first time.Ethnobotanical data were collected from 92 local informants through semi-structured questionnaires, open interviews, and field surveys during a period of two years (2018-2020). The statistical analysis included use reports (UR) for each species, and informant consensus factor (FIC) to evaluate the data.In the present study a total of 156 plant species belonging to 58 botanical families, were recorded for the treatment of 16 diseases categories. The most represented families were Lamiaceae, followed by Asteraceae, and Apiaceae. The most frequently cited plant species with the highest use report (UR) were Pistacia atlantica (161), Hymenocrater longiflorus (128), Melissa officinalis (124), Cyperus rotundus (114), Thymus transcaspicus (112), and Quercus brantii (109). Psychological (ICF = 0.96), musculoskeletal (ICF = 0.94), and digestive (ICF = 0.93), followed by respiratory problems (ICF = 0.92) showed the highest informant consensus factors among all ailment categories. Most herbal remedies were consumed as decoction. Leaves (28.5%) were the most widely used plant parts, followed by flowers (18.7%), aerial parts (14.5%), seeds (13.2%), and terrestrial parts (8.41%). Some interesting new medicinal uses for native and common species were reported. Species such as Cyperus rotundus, Hymenocrater longiflorus, Anthriscus nemorosa, Pistacia atlantica and Quercus brantii would be interesting targets for drug discovery and are suggested for further investigations.The plant use reports, and quantitative data analyzed demonstrate that the relative importance of plant species and shared knowledge of herbal therapies among Kurdish communities of the Sarvabad county is still rich. A systematic study and evaluation of the biological activity of highly consumed plants, could identify the possible mechanism of action.

Ustukhuddus Alavi is a polyherbal formula which is introduced by Persian medicine scholars. It is traditionally used to treat brain disorders and is claimed to do so by preprocessing and cleansing the waste products from the brain. According to Persian medicine, the disposal of brain waste products is necessary for optimal cognitive performance.Sustaining optimal cognitive performance is crucial for ideal quality of life and higher academic achievements in high school students. The objective of this study was to determine the effects of this multi-component herbal product on the cognitive performance and salivary cortisol levels of adolescent female students.The effect of a 6-week randomly assigned Ustukhuddus Alavi versus placebo administration on cognitive performance was assessed by the paced auditory serial addition test (PASAT) at the baseline and after the 3- and 6-week intake of Ustukhuddus Alavi or placebo and the one-month follow-up in 86 healthy female high school students in grades 10 and 11. Additionally, we measured the levels of salivary cortisol of the students pre- and post-intervention.Significant mean difference between the Ustukhuddus Alavi and placebo groups in three of the paced auditory serial addition test (PASAT) subscales, namely mental health (p-value = 0.006), sustained attention (p-value = 0.001) and mental fatigue (p-value = 0.001), were observed after six weeks. We also found a significant difference between the mean salivary cortisol level of the two groups after the intervention (p-value = 0.047).These findings reveal that the intake of the multi-ingredient herbal product Ustukhuddus Alavi for six weeks can be helpful for cognitive function and cortisol levels in female high school students. These positive effects seem to be related to the increase in sustained attention and the decrease in mental fatigue.

Carthamus tinctorius L. (Safflower) has been widely recommended to treat metabolic disorders in traditional herbal medicine in Persia, China, Korea, Japan, and other East-Asian countries. The anti-hypercholesterolemic and antioxidant effects of this plant have been well documented, but its protective effects against Metabolic Syndrome (MetS) have not been fully illustrated.The present study aimed to evaluate the effects of safflower oil on MetS risk factors.In this randomized, double-blind, placebo-controlled clinical trial, 67 patients with MetS were administered either divided 8 g safflower oil or placebo daily for 12 weeks. All patients were advised to follow their previous diets and physical activities.Safflower oil resulted in a significant reduction in waist circumference (-2.42 ± 3.24 vs. 0.97 ± 2.53, p0.001), systolic blood pressure (-8.80 ± 9.77 vs. -2.26 ± 8.56, p = 0.021), diastolic blood pressure (-3.53 ± 7.52 vs. -0.70 ± 6.21, p = 0.041), fasting blood sugar (-5.03 ± 10.62 vs. 2.94 ± 7.57, p = 0.003), and insulin resistance (-0.59 ± 1.43 vs. 0.50 ± 1, p = 0.012), but an increase in adiponectin level (0.38 ± 0.99 vs. -0.09 ± 0.81, p = 0.042) in the treatment group in comparison to the placebo group. The results revealed a direct relationship between leptin level and Body Mass Index (BMI) in both groups (p0.001). In addition, increase in BMI resulted in a non-significant decrease in adiponectin level in both groups. Moreover, no significant difference was observed between the two groups regarding lipid profiles, leptin serum level, serum creatinine concentration, and other outcomes.Safflower oil without lifestyle modification improved abdominal obesity, blood pressure, and insulin resistance in patients with MetS.

Ethnopharmacological relevance The diaphragma juglandis (DJ) comes from the wooden septum in the core of Juglans regia L, also known as the walnut septum. In Iranian traditional medicine, walnut distraction wood was widely used in the treatment of diabetes. However, there is a lack of research data on the mechanism of DJ against diabetes. Aim of the study: To explore the protective effect of diaphragma juglandis extract (DJE) on type 2 diabetic rats and the hypoglycemic mechanism of DJE. Material and methods Supplemented DJE and fed a high-fat diet for five weeks, and then injected low-dose STZ, successfully induced type 2 diabetic rats. Collected rat serum, liver, pancreas and feces to determine the biochemical parameters of serum and liver, analyze the pathological damages of pancreas and liver, and measure the changes of gut microbes in feces. Results DJE could inhibit the metabolic abnormalities of T2DM by improving insulin resistance, abnormal lipid metabolism, liver damage, oxidative stress, and reducing inflammation. DJE significantly held fasting blood glucose, glycosylated serum protein, serum low density lipoprotein, high density lipoprotein, oral glucose tolerance test, nitric oxide, superoxide dismutase and catalase, serum and liver triglycerides, total cholesterol, aspartate aminotransferase, alanine aminotransferase, malondialdehyde, lipopolysaccharide, fasting insulin and tumor necrosis factor-α and prevented the pathological damage of pancreas and liver. The 16SrRNA gene sequencing results showed that DJE intercepted the disorders of the fecal gut microbes, mainly including Lactobacillaceae, Rikenella, Pygmaiobacter, Oscillospiraceae and Klebsiella. Spearman correlation analysis showed that the changes of gut microbes were closely relative with biochemical parameters. Conclusion DJE might prevent type 2 diabetes and its complications and hold up the disorders of gut microbes.

Background: Vitiligo is a hypopigmentation disorder that affects 1% of the world's population. Vitiligo causes white spots on the skin, mucous membranes, or white hair by destroying skin melanocytes. The pathogenesis of vitiligo is unknown but autoimmune, autocytotoxic, and neural mechanisms are suggested. According to the autoimmune theory, in people with vitiligo, immune cells invade and damage melanocytes. T cells are more commonly present in vitiligo patients' skin and remain in the lesion site, which is composed of CD8 and CD4 T cells. Many studies have been conducted on the presence and role of cytokines such as interleukins and interferongamma (IFN-γ) in the vitiligo process. Aim: This study aimed to introduce herbs effective against vitiligo from the perspective of Persian medicine and to investigate their possible therapeutic mechanisms with the possible effects of herbs on autoimmune mechanisms. Methods: For this purpose, keywords were used to extract data from Persian medicine textbooks, and then relevant scientific databases, including Google Scholar, PubMed, Web of Science, and Scopus were examined. Results: It was found that Persian medicine scholars used 50 different medicinal plants to treat and reduce the complications of vitiligo, and recent scientific studies have proven immune-regulating properties and reducing the effect of many of them on cytokines. Conclusion: According to scientific evidence on immunomodulatory effects, new research into the effects of these plants on vitiligo can lead to the discovery of new drugs and approaches for treating this disease.

Sciatica is a common back pain caused by irritation of the sciatic nerve. Current pharmacologic therapies have proven inadequate for many patients with sciatic pain. On the other hand, there is a globally increasing demand for the use and administration of natural medicaments for this disorder. Traditional Persian Medicine (TPM) is a school of medicine and a medicinal plant-based resource for clinical studies put forward by Persian scholars. The aim of the present study is to gather and study the effectiveness of all medicinal plants from five main Persian pharmacopeias. Furthermore, different databases such as PubMed and Scopus have been checked to derive relevant activities for these plants. In all, 99 medicinal plants related to 42 families have been authenticated. Asteraceae and Apiaceae were the most frequent families and roots and seeds were the most reported botanical parts. The employed routes of administration were oral (54%), topical (33%) and rectal (13%). Anti-inflammatory, analgesic activity and antinociceptive properties of medicines are known as some main mechanisms to manage sciatic pain. These functions are possessed by 30%, 15%, and 15% of the studied plants, respectively. Medicaments that can be introduced as lead agents for further investigation are Zingiber officinale Roscoe, Olea europaea L., Strychnos nux-vomica L and Artemisia vulgaris L which showed all of these properties in previous studies. Hence, conducting adducible clinical trials using these lead agents may lead to novel drugs with lesser undesirable and much more therapeutic effects on controlling sciatic pain.

Background: Cancer is one of the most prevalent diseases associated with heavy complications in treatment. Mucotoxic cancer therapies such as head and neck radiotherapy and some of the chemotherapy agents may lead to oral mucositis. In addition to its economic consequences, mucositis also affects patients' quality of life. In Traditional Persian Medicine (TPM) manuscripts, several medicaments have been suggested for the treatment of mucositis. Objective: Considering the public welcome for herbal medicine, the current evidence-based review study is conducted to investigate the herbal remedies which have been proposed for oral mucositis in TPM. Methods: At first, a comprehensive survey was done on Qanon fi al-Teb, which is the most important textbook of TPM; then the scientific name of the herbs was authenticated according to the botanical textbooks. At last, data banks including Scopus, Pubmed, Web of science and Science direct were investigated for possible relevant properties of each medicinal plant in the literature. Results: In total, 30 herbs are introduced in this study. According to the registered documents, 18 herbs are reported to have antioxidant, anti-inflammatory, antimicrobial, anti-nociceptive and wound healing properties of which the therapeutic effect of only a few herbs including Glycyrrhiza glabra, Malva sylvestris, Morus nigra, Punica granatum, and Solanum nigrum were directly evaluated against oral mucositis on the literature. Conclusion: Despite the lack of human studies on mucositis for the other discussed herbs, their related pharmacological properties can be considered for new natural drug discovery supported by medieval and traditional experiments.