Hypericum perforatum L. and the Underlying Molecular Mechanisms for Its Choleretic, Cholagogue, and Regenerative Properties.

Any defects in bile formation, secretion, or flow may give rise to cholestasis, liver fibrosis, cirrhosis, and hepatocellular carcinoma. As the pathogenesis of hepatic disorders is multifactorial, targeting parallel pathways potentially increases the outcome of therapy. Hypericum perforatum has been famed for its anti-depressive effects. However, according to traditional Persian medicine, it helps with jaundice and acts as a choleretic medication. Here, we will discuss the underlying molecular mechanisms of Hypericum for its use in hepatobiliary disorders. Differentially expressed genes retrieved from microarray data analysis upon treatment with safe doses of Hypericum extract and intersection with the genes involved in cholestasis are identified. Target genes are located mainly at the endomembrane system with integrin-binding ability. Activation of α5ß1 integrins, as osmo-sensors in the liver, activates a non-receptor tyrosine kinase, c-SRC, which leads to the insertion of bile acid transporters into the canalicular membrane to trigger choleresis. Hypericum upregulates CDK6 that controls cell proliferation, compensating for the bile acid damage to hepatocytes. It induces ICAM1 to stimulate liver regeneration and regulates nischarin, a hepatoprotective receptor. The extract targets the expression of conserved oligomeric Golgi (COG) and facilitates the movement of bile acids toward the canalicular membrane via Golgi-derived vesicles. In addition, Hypericum induces SCP2, an intracellular cholesterol transporter, to maintain cholesterol homeostasis. We have also provided a comprehensive view of the target genes affected by Hypericum's main metabolites, such as hypericin, hyperforin, quercitrin, isoquercitrin, quercetin, kaempferol, rutin, and p-coumaric acid to enlighten a new scope in the management of chronic liver disorders. Altogether, standard trials using Hypericum as a neo-adjuvant or second-line therapy in ursodeoxycholic-acid-non-responder patients define the future trajectories of cholestasis treatment with this product.

Burn Wound Healing Effect of a Sterilized Traditional Formulation of Boswellia carteri vs. Silver Sulfadiazine Cream 1% in Patients Presenting Second-degree Burn Wounds: A Randomized, Double-blind Clinical Trial.

Background: Burn wounds rank among the most serious healthcare issues. Many studies reported the effectiveness of natural products in the wound-healing process. The present study compared the effects of a standardized herbal formulation derived from Boswellia carteri (B. carteri) and silver sulfadiazine (SSD) cream 1% on the healing of burn wounds. Methods: This randomized double-blind clinical trial was conducted at Shiraz Burn Hospital (Shiraz, Iran) between July 2012 to August 2013. A sterilized formulation comprising B. carteri 40% was prepared. 54 second-degree burn patients of both sexes with age ranges of 20 to 60 were invited to participate in this double-blind, randomized clinical trial. They were randomly divided into two groups and given either the Boswellia formulation or SSD cream. The healing index was determined based on the wound area assessment using the planimetry technique. The Kaplan-Meier survival analysis was used to assess the primary outcome, which was the amount of time until complete healing. Results: The trial was completed by 17 patients from the SSD group and 15 patients from the Boswellia group. During the study period, both groups showed a progressive healing trend. The mean (95% CI) healing time in the SSD group was 10.94 (9.03-12.85) days and 10.73 (9.23-12.23) days in the Boswellia group (P=0.71), indicating no significant difference. On the 17th day, the healing index of all patients in the Boswellia group reached 1. Conclusion: Boswellia topical formulation had a burn wound healing effect comparable to that of the standard SSD 1% treatment. Based on the findings of this study, the likelihood of contact dermatitis with Boswellia should be taken into consideration.

Startup-Based Learning as an Innovative Method for Pharmacy Education: Medicinal Plants Course Model.

Background: Familiarizing students with knowledge-based businesses is one of the goals emphasized in the developed educational systems worldwide. This study aimed to design a startup-based learning model (SBL). Methods: As a qualitative research study, startup teams were formed by the pharmacy students of Shiraz University of Medical Sciences in 2020. This model was used to train 120 students as pharmaceutical entrepreneurs through related lectures, simulations, and field activities. We employed this model for students to become familiar with the various stages of examining market needs, knowledge-based company registration, intellectual property, logo design, and even pharmaceutical product development. Students' feedback was assessed with a questionnaire designed by the team of researchers, and its results were used to analyze the course and improve the quality of the proposed model. Results: Most of the studied indices revealed that the students rated this model as good or excellent. Satisfaction with more important indices includes student creativity and ideation in educational activity (60.7%), attractive presentation (60.4%), teamwork among learners (62.2%), appropriateness of evaluation method (65.4%), understanding how to make herbal remedies (49.1%), learner participation in the educational activity (74.8%), entrepreneurial motivation (60.7%), and applicability (64.4%). Conclusion: We found this model effective in boosting students' satisfaction, creativity, and entrepreneurial spirit. Lecturers also play a facilitator role in addition to specialized training. Therefore, in this model, both lecturers and students can grow more and make education more attractive. This study, for the first time, demonstrated that SBL could be applied in education systems and make the students more interested in educational content and help them to prepare for the job market.

Preserving effect of Loboob (a traditional multi-herbal formulation) on sperm parameters of male rats with busulfan-induced subfertility.

OBJECTIVE: Male infertility secondary to exposure to gonadotoxic agents during reproductive age is a concerning issue. The aim of this experimental study was to determine the effect of Loboob on sperm parameters. METHODS: 55 healthy rats were selected, weighted and divided into five groups consisting of 11 rats each. The control group received no medication. Rats in Treatment Group 1 received 10mg/kg Busulfan and rats in Treatment Groups 2, 3, and 4 received 35,70 and 140 mg/kg Loboob respectively in addition to 10mg/kg Busulfan. Finally, the sperm parameters and weights of the rats were compared using the Kolmogorov-Smirnov, non-parametric Kruskal-Wallis, and Dunn-Bonferroni tests. RESULTS: All sperm parameters and weights were significantly decreased among rats receiving Busulfan. All dosages of Loboob were effective to enhance the motility of slow spermatozoa, while only in the rats given 70 and 140 mg/kg of Loboob saw improvements in progressively motile sperm percentages (0.024 and 0.01, respectively). Loboob at a dosage of 140mg/kg improved sperm viability. It did not improve normal morphology sperm or decrease immotile sperm counts. Loboob did not affect mean rat weight. CONCLUSIONS: Loboob offered a dose-dependent protective effect on several sperm parameters in rats with busulfan-induced subfertility.

Potentials of Antitussive Traditional Persian Functional Foods for COVID-19 Therapy†.

Coronavirus disease 2019 is a worldwide pandemic resulting in a severe acute respiratory syndrome. Remdesivir is the only FDA-approved drug for hospitalized patients older than age 12. It shows the necessity of finding new therapeutic strategies. Functional foods (FFs) could have co-therapeutic and protective effects against COVID-19 infection. Traditional Persian medicine (TPM), one of the safest and most popular schools of medicine for hundreds of years, has recommended potential FF candidates to manage such a global pandemic. To reveal the potential of TPM in terms of antitussive FFs, traditional Persian pharmacopoeia "Qarabadin-e-Salehi" was searched using the keywords "Soaal" and "Sorfeh." Also, a search of MEDLINE, PubMed Central, Google Scholar, and Science Direct was performed for the relevant literature published from the inception up to March 2021. A combination of search terms including "cough, antitussive, antioxidant, anti-inflammation, antiviral, COVID-19, mucoactive, mucolytic, expectorant, and mucoregulatory" was also applied. The potential mechanism of action in SARS-CoV-2 infection was discussed. Twelve TPM FFs were found including Laooqs, Morabbas, a Saviq, a soup, and a syrup. They are combinations of two to seven ingredients. Natural compounds of mentioned formulations have the main pharmacological mechanisms including antiviral, anti-inflammatory, antioxidant, antihistamine, bronchodilator, immunomodulatory, and mucoactive effects as well as central or peripheral antitussive activities. FFs are cost-effective, easily accessible, and safe options for both treatment and prevention of COVID-19. They might have positive psychological effects along with their pharmacological effects and nutritional virtues. They could also manage persistent respiratory discomforts after recovery from COVID-19.

Effect of a novel herbal vaginal suppository containing myrtle and oak gall in the treatment of vaginitis: a randomized clinical trial.

BACKGROUND: Uncomplicated infections such as candidiasis, bacterial vaginosis (BV), or trichomoniasis are easy to diagnose and treat. However, about 8% of patients will have a more complicated course with failure to respond to treatment or rapid recurrence of symptoms. There are many suggestions in Traditional Persian Medicine like myrtle (Myrtus communis L.) and oak gall (Quercus infectoria G.Olivier) for treatment of vaginitis. OBJECTIVES: A clinical trial was designed to assess the efficacy of a novel herbal suppository, containing myrtle and oak gall (MOGS) in treatment of vaginitis. METHODS: In a parallel randomized clinical trial, 120 women with vaginitis were randomly assigned to MOGS, metronidazole, or placebo. Formulation was simulated from traditional Persian manuscripts and MGOS was prepared after pharmaceutical optimization processing as well as quantification of gallic acid by HPLC. The study was double-blind for MOGS and placebo and single-blind for metronidazole group. RESULTS: MOGS effectively improved vaginal discharge (p = 0.024 for BV and 0.018 for trichomoniasis) and pH (compared to placebo (p = 0.013) and metronidazole (p = 0.001)). Both MOGS and metronidazole could reverse whiff test. Metronidazole was the best medication for making Nugent score negative (p = 0.005) as well as the best therapy according to laboratory findings to treat BV in comparison with placebo (p = 0.021). While for trichomoniasis, MOGS could improve the disease more successfully (p = 0.001). Both MOGS and metronidazole treated mixed vaginitis (p = 0.002). CONCLUSION: MOGS would be a chance for developing new treatment for trichomoniasis.

Traditional neurotherapeutics approach intended for direct nose to brain delivery.

ETHNOPHARMACOLOGICAL RELEVANCE: Nasal delivery systems have a significant role in Persian traditional medicine. Most of them were utilized for central nervous system (CNS)-related disorders. In modern medicine, nasal drug delivery systems for brain delivery are highly regarded. AIM OF THE STUDY: Despite recent advances in drug delivery to the (CNS), delivery of therapeutics to the brain remains a major challenge because of the blood brain barrier (BBB). There are several mechanisms which regulate the drug transfer across the BBB. Local administration methods of therapeutic agents are often associated with adverse events, while the intranasal pathway has been suggested as a non-invasive alternative route to deliver drugs to the brain. This route can bypass the BBB and deliver drug molecules directly to the CNS. There are different nasal formulations have been addressed in Persian traditional pharmacopeias. The present review attempt to explore the famous and practical Qarabadin to find ancient nasal dosage forms. MATERIALS AND METHODS: With an explore on traditional herbs in google scholar, scopus and science direct, we have found some original and review articles which have demonstrated our findings on the use of traditional herbs for CNS disorders. Four encyclopedia of multi-component formulations, including Qarabadin Salehi (1766), Qarabadin kabir (1781),Qarabadin Ghaderi (18th century), and Qarabadin Azam (1853), were searched for nasal formulations having CNS-related indications. Formulations were categorized based on dosage forms, and also, diseases which they were suggested for. While the names of illnesses were in ancient terminology of Traditional Medicine, they were translated to modern medical terminology by comparing their definitions, signs, and symptoms from two medical systems. Typical samples of each dosage form have been mentioned with details like amount of ingredients, scientific names of plants, and considerations pertaining to preparation or usage. RESULTS: Among all traditional nasal formulations, seven types were found that is used for sicknesses relating to CNS including Saoot, Nafookh, Atoos, Nashoogh, Shamoom, Lakhlakheh, and Bakhoor. CONCLUSIONS: The findings of this study reveal the physicochemical characteristics of each formulation, route of administration, and type of disease which they are suitable and also present some famous formulations.

Qairooti (Cerate or Cera Beeswax Salve) in Traditional Iranian Pharmacy.

BACKGROUND: Qairooti (Cerate), a medicinal salve or ointment, compounded of wax and oil, is a formulation used alone or as a basis for medicinal dosage forms. It is widely used from the ancient times to the present. Based on its structure, beeswax has unique characteristics. It builds stable emulsions and increases water absorbance of creams and ointments. The aim of this study was to gather all pharmaceutical information about preparing Qairooti products from traditional pharmacopoeaes, such as the various types of Qairooti and their preparation methods. METHODS: In this article, various types of Qairooti, their producing method and related indications have been discussed based on the main medical Persian manuscripts including Al-Canon fil tibb (Canon of Avicenna), Gharabadin-e-Kabir, Gharabadin-e-Salehi, Exir-e-Azam, Alhavi, Kamel-al-sanaat, Zakhireh-ye Khwarazm shahi, al-Shamel-fi-sanawat-al-tebie, Ekhtiarate badiee, Kholasat-al-tajarob, Tib-e-Akbari, Mofareh al-gholoob, Makhzan-ul-Adwiah, Hedayat-al-motealemin-fi-al-tibb, Altasrif-le-man-ajeza-an-talif, etc. RESULTS: About 500 different formulations from the above-mentioned manuscripts were found and their preparation method and other required information were collected. The amounts of oil and wax in Qairooti are not fixed and depend on different factors; providing the best consistency and appearance of the formulation, such as seasonal temperature. In order to prepare cerate, wax has to be melted by indirect heat and then mixed with the isothermal oil. Mixing process should be performed precisely to provide a homogenized product. If the multi-ingredient cerate is needed, other constituents have to be added to the warm mixture of oil and wax. CONCLUSION: There are many kinds of Qairooti in traditional Iranian pharmacopoeias recommended for different indications. Cerate was a common medication for injuries and wounds. Although it is still used in conventional medicine, some clinical applications in traditional Iranian medicine have been forgotten nowadays. It is recommended that we have a smarter approach to the traditional pharmacopoeias in order to use past experience and transcend existing knowledge of modern pharmacy.

The Introduction of Submitted Approaches in Iranian Traditional Medicine for Treatment of Diabetes.

BACKGROUND: Diabetes mellitus is a complex disorder of carbohydrate metabolism. According to past studies, the word ziabites in Iranian traditional medicine (ITM) correlate with diabetes. The aim of this study was to identify the definition, therapeutics, and mechanism of diabetes from the resources of ITM in order to provide new recommendations for the treatment of diabetes. METHODS: We searched therapeutic ITM books such as Exir-e-Aazam, Tibib-e-Akbari, as well as material medical ITM books such as Makhzan-ol-Advieh and Tohfat-ol-momenin to find topics on ziabites. We also searched ScienceDirect and PubMed databases with keywords "herbal medicine" and "diabetes" to confirm the effectiveness of the reported methods. RESULTS: We identified 17 ITM books that referred to ziabetes. We also determined that there were different mechanisms and dosage forms for the management of ziabites. The number of materials related to ziabites mechanisms in Makhzan-ul-Adwiah was 138. For instance, Asperugo procumbens amplifies liver and Cucurbita maxima diminish kidney temperature. Forms of administration recommended in Eksir-e-Aazam include oral, inhalation, rectal and topical; among which oral and inhalation have been verified by conventional medicine. We also found articles that substantiated the antidiabetic effect of some medicinal herbs mentioned in Exir-e-Aazam. CONCLUSION: There are several forms of administration recommended in ITM for the treatment of diabetes, which have not been used in conventional medicine. Hence, reported solutions can be analyzed for the management of diabetes. Notably, there are many herbs mentioned in ITM that remain to be studied. Therefore, further studies are required to substantiate their effects scientifically in order to develop new effective drugs.

Knowledge of burn wound healing: the heritage from traditional pharmacy of Persia.

The traditional pharmacy of Persia is based on numerous ancient manuscripts written by the elites of medicine and pharmacy. These references which belong to different centuries (mostly from the 9th to 19th century) represent vast information about pharmaceutical and therapeutic knowledge. Studying these works could be valuable in revealing the hidden parts of the history of science, especially pharmacy and medicine. Also, modernisation of the methods of treatment and the majority of formulations seems to be possible. It is obvious that setting ancient experiences besides recent studies makes pharmacists and physicians more powerful. This review aims to introduce traditional knowledge about different treatments for burn wounds which has been extracted from various Persian manuscripts.