Medicinal Importance of Ajuga Species in Iran: Ethnobotanical and Traditional Applications, Phytochemical, and Pharmacological Studies

Context: Five species of the genus Ajuga (Lamiaceae) having the common name of "bugle" are found in Iran. In Persian medicine (PM), the genus Ajuga (Kamaphytus) is used for treating jaundice, joint pain, gout, amenorrhea, sciatica, and wound healing. This study aimed to review the ethnobotanical, phytochemical, and biological activities of Ajuga species that grow in Iran to determine their therapeutic potentials and suggest further studies on the healing properties of this genus in Iran. Evidence Acquisition: Electronic databases such as PubMed, Scopus, and Google Scholar were comprehensively searched for studies on Ajuga species in Iran, including "Ajuga austro-iranica," "Ajuga chamaecistus," "Ajuga comata" (Syn.: "Ajuga Chia," "Ajuga chamaepitys subsp. Chia"), "Ajuga orientalis," and "Ajuga reptans." The search period was from 1966 to February 2021. The related articles were selected according to the inclusion and exclusion criteria of the current study. Results: Several ethnobotanical and pharmacologic reports have verified the traditional uses of the genus Ajuga for anti-inflammatory, hypoglycemic, hypolipidemic, analgesic, anabolic, anti-arthritis, antipyretic, and hepatoprotective activities. Numerous phytochemicals have been identified from Ajuga species involving phytoecdysteroids, neo-clerodane-diterpenes, iridoids, flavonoids, withanolides, phenylethyl glycoside, and essential oils. Conclusions: Due to the beneficial therapeutic effects of Ajuga genus, it can be considered in future clinical studies as a source of natural antioxidants, dietary supplements in the pharmaceutical industry, and stabilizing food against oxidative deterioration.

Explanation of Structure and Function of kv1.3 Potent Blocker From Mesobuthus eupeus Venom Gland: A New Promise in Drug Development

Background: Scorpions and other venomous animals are sought with great concern because venom is a source of novel peptides with exciting features. Some toxins of scorpion venom are effectors of potassium channels. Previous studies strongly support the importance of potassium channel toxins for use as pharmacological tools or potential drugs. Objectives: Here, a three-dimensional (3-D) structure and function of a potent acidic blocker of the human voltage-gated potassium ion channel, Kv1.3, previously identified in the scorpion Mesobuthus eupeus venom gland, were interpreted. Methods: The 3-D structure of meuK2-2 was generated using homology modeling. The interaction of meuK2-2 with the Kv1.3 channel was evaluated using a computational protocol employing peptide-protein docking experiments, pose clustering, and 100 ns molecular dynamic simulations to make the 3-D models of the meuK2-2/Kv1.3 complex trustworthy. Results: A CSα/β (cysteine-stabilized α-helical and β-sheet) fold was found for the 3-D structure of meuK2-2. In a different mechanism from what was identified so far, meuK2-2 binds to both turret and pore loop of Kv1.3 through two key residues (Ala28 and Ser11) and H-bonds. The binding of meuK2-2 induces some conformational changes to Kv1.3. Eventually, the side chain of a positively charged amino acid (His9) occupies the channel's pore. All together blocks the ion permeation pathway. Conclusions: MeuK2-2 could block Kv1.3 by a new mechanism. So, it could be a unique target for further investigations to develop a pharmacological tool and potential drug.

Medicinal Plants with Abortifacient or Emmenagogue Activity: A Narrative Review Based on Traditional Persian Medicine

Introduction: Traditional Persian medicine (TPM) has a rich background and has introduced various plants with abortive or emmenagogue activity since ancient times. However, many of them are unknown in modern medicine, and a few trials have been conducted describing their efficacy and safety. These plants may be helpful for the management of incomplete abortion, with potentially lower side effects than chemical agents. Objectives: This review introduced these plants and their potential efficiency to link traditional and modern medicine and suggested further studies. Methods: The search strategy for citations in this narrative review was performed in two steps. At first, medicinal plants used as abortifacient or emmenagogue to manage incomplete abortions or retained products of conception were searched and extracted in the most famous TPM literature, including Al-Qanun Fi at-Tibb, Tuhfat-al-Momenin, and Makhzan-ul-advia. The next step was searching electronic databases including PubMed, Scopus, Web of Science, and Google Scholar with the same keywords and herbal plants between 1970 and 2021. The overlapped plants between the manual and electronic search were found and briefly described. Results: In TPM literature, 88 plants with abortifacient activity were found, of which 47 were used to manage incomplete abortions or retained products of conception. Also, in the electronic database search, 14 plants were found to have abortifacient or emmenagogue activity. Among them, six plants, including Sesamum indicum L. (Sesame), Commiphora myrrha (myrrh), Lawsonia inermis L. (Henna), Opopanax chironium L. (Jooshir), Plumbago rosea (Shitraj or Stumbag), and Juniperus sabina (Abhal), overlapped with the manual search results. The abortifacient or emmenagogue activity and properties of all these 14 plants were described. Conclusions: The properties of many traditional plants with abortifacient activity are unknown in modern medicine; however, they should not be used in pregnant women. Nonetheless, they may have the power to be entered into modern medicine. Identifying their pharmacology and action mechanisms may be helpful to introduce them as a potential alternative to chemical agents in the management of induced or incomplete abortion with possibly lower side effects.

Antifungal Susceptibility of Aspergillus flavus, Aspergillus ochraceus, and Fusarium graminearum to Ganoderma lucidum Extract

Background: Ganoderma lucidum is a well-known fungus that has been widely used in traditional medicine around the world, especially in East Asia, due to its various health promotion properties. Recently, researchers have drawn attention to the biologically active compounds found in this fungus, and this fungus has become very popular due to its pharmaceutical properties. Objectives: The aim of this study was to investigate the antifungal properties of the Iranian strain of G. lucidum as a natural antifungal agent against harmful filamentous fungi common in the food industry. Methods: Three filamentous fungi, including Aspergillus flavus, Aspergillus ochraceus, and Fusarium graminearum, were used in this study for the antifungal evaluation of ethanolic, hydroalcoholic, and two aqueous extracts of G. lucidum with different concentrations by the broth microdilution method. Results: The results showed that only the ethanolic and hydroalcoholic extracts completely inhibited the growth of A. flavus at 2 and 3.5 mg/mL, respectively. Also, no antifungal activity was observed for the aqueous extract for all the three studied fungi. In addition, A. flavus was found to be more sensitive to G. lucidum extracts compared to the two other studied fungi. Conclusions: The ethanolic extract of G. lucidum was effective on A. flavus and can be used as a natural antifungal agent to prevent the growth of this harmful filamentous fungus.

Comparison of Topical Herbal Cream and 1% Clindamycin Gel for Treatment of Mild-to-moderate Acne: A Randomized Clinical Trial

Background: Acne is the most common chronic skin disease affecting young adults and adolescents worldwide. A characteristic of this disease is the chronic inflammation of sebaceous glands leading to comedones, papules, pustules, nodules, and cysts. Topical and systemic uses of medicines are common approaches to treat acne. However, these medicines are associated with some adverse effects and increased microbial resistance. Objectives: We aimed to prepare and apply an herbal formulation containing several herbs with different effects on mechanisms associated with acne formation. Methods: In this study, 66 patients with mild-to-moderate acne randomly received a packet containing herbal medicine or clindamycin gel. The treatment period was two months, and the total acne lesions and acne severity index were measured every four weeks. After eight weeks of treatment and follow-up, the physician examined clinical outcomes and possible complications. Results: Decreases in total acne lesions and acne severity index were significantly different in both treatment groups (P < 0.05 in both groups). Although the herbal cream provided better improvement than clindamycin, there was no significant difference between the two groups (P > 0.05). Conclusions: The use of the herbal cream could be recommended for treating acne lesions due to few complications, greater patient satisfaction, and avoiding microbial resistance to chemical antimicrobials.

Zingerone Attenuates Methotrexate-Induced Hepatotoxicity in Rats

Background: Methotrexate (MTX) is mainly used for the chemotherapy of different types of malignancy and some autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease. The MTX application is limited by its severe side effects, including several types of hepatic injury. Objectives: In this study, we decided to evaluate if zingerone (the main constituent of ginger) can reduce the hepatic side effects of MTX. Methods: Thirty-five rats were divided into five groups: Control group receiving normal saline (N/S), once daily, by gavage, for 10 days, and N/S intraperitoneally (i.p.), a single dose on the ninth day; Methotrexate (MTX) group receiving N/S, once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day; Groups 3 (ZG25), 4 (ZG50), and 5 (ZG100) receiving zingerone (25, 50, and 100 mg/kg, respectively), once daily, by gavage, for 10 days, and MTX (i.p.), a single dose (20 mg/kg) on the ninth day. Results: The results showed a significant decrease in serum AST, ALT, and ALP, as well as the hepatic content of MDA, NO, PC, TNF-α, and IL-1β, in the ZG groups compared with the MTX group. The activity of SOD, CAT, and GPX, as well as the hepatic content of GSH, showed a significant increase in the ZG groups compared with the MTX group. Histopathological improvement in the hepatic tissue of ZG groups compared with the MTX group confirmed all other findings. Conclusions: It is concluded that zingerone can improve hepatic injury induced by MTX in rats regarding the redox system features, inflammation, and histological changes. This can make humans hopeful for using Ginger in the future for attenuating the hepatic side effects of MTX when used chronically.

Renoprotective Effect of Fucoidan from Seaweed Sargassum angustifolium C. Agardh 1820 on Gentamicin-Induced Nephrotoxicity: From Marine Resources to Therapeutic Uses

Background: Nephrotoxicity is a major side effect of aminoglycoside antibiotics, caused by oxidative damage and inflammation. Fucoidan, a group of sulfated polysaccharides derived from different species of brown algae, are well recognized for their antioxidant and anti-inflammatory activities. Objectives: In the present study, we aimed to investigate, for the first time, the efficacy of fucoidan extracted from Sargassum angustifolium C. Agardh 1820 against gentamicin-induced nephrotoxicity in rats. Methods: Twenty-eight male Wistar rats were divided into 4 groups of control, gentamicin (100 mg/kg), and gentamicin plus 50- and 100-mg/kg/day fucoidan pretreatment. In the end, all rats were killed, and then urine, blood, and tissue samples were prepared. Kidney weight (KW), body weight (BW), and 24-hour urine volume, as well as serum creatinine (Cr), blood urea nitrogen (BUN), Cr clearance, and malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity, were measured. Kidney samples were also evaluated for histopathological changes. Results: Gentamicin significantly increased KW, KW/BW ratio, 24-hour urine volume, serum Cr, MDA, and BUN levels; however, fucoidan pretreatment, especially at a dose of 50 mg/kg, significantly returned these variables near to the control group values. Gentamicin also decreased BW gain, Cr clearance, SOD activity, and the degree of renal tissue damage compared to the control group, while treatment with fucoidan significantly reversed these alterations. Conclusions: The results show that fucoidan from S. angustifolium C. Agardh 1820 ameliorates gentamicin-induced nephrotoxicity by alleviating oxidative stress and augmenting antioxidant enzymes activity in renal tissue, suggesting the potential use of this fucoidan in a clinical setting.

Comparing the Effects of Two Cream Formulations, Henna (Lawsonia inermis) and Clotrimazole, on Vaginal Candidiasis: A Randomized Controlled Trial

Background: Vaginal candidiasis is the most prevalent infection among reproductive-aged women. The current treatment for this disorder includes azole compounds. Objectives: The aim of this study was to compare the effects of two creams, henna (Lawsonia inermis) and clotrimazole, on vaginal candidiasis. Methods: In this trial, 80 women with vaginal candidiasis were recruited and randomly assigned into two groups to receive either henna (n = 40) or clotrimazole (n = 40) for one week. The ethanol extract of henna was prepared. Vaginal discharge was cultured, and vaginal pH, colony formation, lactobacillus formation, and vaginitis subjective symptoms were evaluated before and one, two, and four weeks after the intervention. The chi-square test, independent t-test, and Generalized Estimating Equations were were used for analyzing the data using SPSS version 22. Results: After four weeks of the intervention, almost 90% of the women in the henna group declared no burning sensation, itching, discharge, irritation, or dyspareunia, while only 45%, 5%, 37.5%, 52.5%, and 27.5% of the participants in the clotrimazole group did not have these symptoms, respectively (P < 0.001). The means (SD) of colony formation were 290.85 (47.35) and 265.12 (37.46) in the henna and clotrimazole groups, respectively, at the baseline, which reduced to zero and 25.45 (25.09) in the 4th week of the intervention (P = 0.001). Compared with the clotrimazole group, there was a significant increase in the mean of lactobacillus formation and a significant decrease in vaginal pH in the henna group (P < 0.001). Conclusions: Henna vaginal cream could significantly reduce the symptoms of vaginal candidiasis, such as burning sensation, itching, discharge, irritation, and dyspareunia. Also, it could decrease colony formation and vaginal pH and increase lactobacillus formation.