Evaluation of the Therapeutic Effect of the Traditional Herbal Medicine Atrifil and Oshagh Gum on Testosterone-Induced Benign Prostatic Hyperplasia in Wistar Rats.

Benign prostatic hyperplasia (BPH) is a common disease that affects elderly men with various complications. This study evaluates the effects of an Iranian traditional herbal medicine "Atrifil and Oshagh gum" on BPH in male Wistar rats. Atrifil is a combination of three medicinal plants: Emblica officinalis Gaertn, Terminalia chebula Retz, and Terminalia bellerica Retz" extracts, and Oshagh gum is Dorema ammoniacum D. Dono gum. In this study, 30 male Wistar rats were divided into five groups: normal control, disease, finasteride, and extract with 300 and 600 mg/kg groups. The extract is a combination of hydroalcoholic Atrifil extract and Oshagh gum. All groups received intramuscular testosterone enanthate to induce BPH except the normal control group. On the twenty-eighth day, prostate glands were separated. Histopathological changes were observed. Furthermore, the prostate-specific antigen (PSA) and prostate weights were measured. The binding propensities of finasteride, equol, and flavonoids present in this extract such as quercetin, rutin, and kaempferol for 5α-reductase, estrogen receptor alpha and beta, and estrogen-related receptor gamma were assessed using in silico docking approach. Histopathological evaluation, biochemical parameter, and PSA level results indicated significant inhibition of accruing and progression of BPH in groups treated with 600 mg/kg extract (p < 0.01). Furthermore, molecular docking showed that rutin had a high affinity to bind the receptors 5α-reductase, estrogen receptor beta, and estrogen-related receptor gamma even more than finasteride, and on average, quercetin had a higher affinity to all these receptors. In the end, it can be concluded that Atrifil and Oshagh gum is effective in preventing BPH.

A Comprehensive Review on the Ethnopharmacology, Phytochemistry, Pharmacology, and Toxicology of the Mandragora Genus; from Folk Medicine to Modern Medicine.

The Mandragora genus (Solanaceae) is well known for its association with myths and has been used in herbal medicine since ancient times. This extensive literature review synthesizes the information currently available on the ethnobotany, Persian medicine (PM), traditional use, phytochemistry, pharmacology, and toxicity profile of Mandragora spp. The electronic search engines Scopus, Web of Science, PubMed, Google Scholar, and ScienceDirect were searched using keywords such as Mandragora, mandrake, phytochemistry, ethnopharmacology, Persian medicine, ethnobotany, and toxicity. Pertinent information was also extracted from books on PM, ethnomedicine, and dissertations. Mandragora species are found throughout the Mediterranean basin, Europe, Northern Africa, and the Himalayan regions. Traditionally, the species have been used to treat insomnia, dysuria, hemorrhoids, rheumatic pain, toothache, melancholia, and depression, among many others. In vitro studies have confirmed the biological properties of Mandragora spp. crude extracts, such as antioxidant, immunomodulatory, and enzyme-inhibiting effects. Various phytochemicals, such as alkaloids (e.g., atropine and scopolamine), coumarins (e.g., umbelliferone and scopoletin), withanolides (e.g., salpichrolide C), and lipid-like compounds (e.g., beta-sitosterol), have been isolated from Mandragora spp. Some of the pure compounds composing this plant are highlighted for their biologically active effects, including anticholinergic, antidepressant, antioxidant, and anti-inflammatory effects. Modern identifications of biological activities of the compounds isolated from Mandragora, especially alkaloids, support its traditional uses (e.g., for their narcotic effects). More in vivo studies are required to further understanding and most effectively utilize this genus, and extensive toxicological studies are required to validate its safety in clinical use.

Naringin and naringenin as anticancer agents and adjuvants in cancer combination therapy: Efficacy and molecular mechanisms of action, a comprehensive narrative review.

Although the rates of many cancers are controlled in Western countries, those of some cancers, such as lung, breast, and colorectal cancer are currently increasing in many low- and middle-income countries due to increases in risk factors caused by development and societal problems. Additionally, endogenous factors, such as inherited mutations, steroid hormones, insulin, and insulin-like growth factor systems, inflammation, oxidative stress, and exogenous factors (including tobacco, alcohol, infectious agents, and radiation), are believed to compromise cell functions and lead to carcinogenesis. Chemotherapy, surgery, radiation therapy, hormone therapy, and targeted therapies are some examples of the approaches used for cancer treatment. However, various short- and long-term side effects can also considerably impact patient prognosis based on clinical factors associated with treatments. Recently, increasing numbers of studies have been conducted to identify novel therapeutic agents from natural products, among which plant-derived bioactive compounds have been increasingly studied. Naringin (NG) and its aglycone naringenin (NGE) are abundantly present in citrus fruits, such as grapefruits and oranges. Their anti-carcinogenic activities have been shown to be exerted through several cell signal transduction pathways. Recently, different pharmacological strategies based on combination therapy, involving NG and NGE with the current anti-cancer agents have shown prodigious synergistic effects when compared to monotherapy. Besides, NG and NGE have been reported to overcome multidrug resistance, resulting from different defensive mechanisms in cancer, which is one of the major obstacles of clinical treatment. Thus, we comprehensively reviewed the inhibitory effects of NG and NGE on several types of cancers through different signal transduction pathways, the roles on sensitizing with the current anticancer medicines, and the efficacy of the cancer combination therapy.

Pulmonoprotective Action of Zataria multiflora Ethanolic Extract on Cyclophosphamide-Induced Oxidative Lung Toxicity in Mice.

OBJECTIVE: To evaluate the protective effect of Zataria multiflora extract, an antioxidative medicinal plant, against cyclophosphamide (CP)-induced oxidative lung damage in mice. METHODS: Mice were intraperitoneally pre-treated with various doses of Zataria multiflora extract (50, 100, 200, and 400 mg/kg) once daily for 7 consecutive days. Animals were then injected with a single 200 mg/kg intraperitoneal dose of CP 1 h after the last administration of O. vulgare. Twenty-four hours later, mice were euthanized, the lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with Zataria multiflora significantly inhibited the elevation of lipid peroxidation level and the depletion in glutathione content, and superoxide dismutase and catalase activities induced by CP in lung. In addition, Zataria multiflora effectively alleviated CP-induced histopathological abnormality and pulmonary damages in mice lung tissues. CONCLUSIONS: The results reveal that Zataria multiflora protects lung tissues from CP-induced toxicity and suggest a role for oxidative stress in the pathogenesis of lung toxicity produced by CP in mice. Because Zataria multiflora has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a good supplement for reducing organ toxicity in patients undergoing chemotherapy, besides their consolidated ethnopharmacological uses.

Effects of some natural products from fungal and herbal sources on Giardia lamblia in vivo.

Giardia lamblia (G. lamblia) is the most widely known protozoan parasite that causes human gastrointestinal infection worldwide. Some natural compounds exhibited pivotal effects against different infectious diseases. In this research, the antigiardial activity and cytotoxicity of fungal chitosan, nano-chitosan, Rhamnus cathartica (R. cathartica) and emodin were evaluated in Balb/c mice. Genotyping of G. lamblia was assessed by PCR-RFLP technique. Different concentrations of mentioned compounds were used to check their antigiardial and cytotoxicity effects on human intestinal epithelial cells (HT-29) after 24, 48 and 72 h. The G. lamblia strain used in the current work was genotyped and revealed as an AII assemblage. All the concentration showed acceptable activity against G. lamblia cysts and trophozoites in comparison to the negative and positive controls (furazolidone and metronidazole) in vitro (P 0.05). The maximum mortality rate (100%) was achieved at 100 and 50 µg kg-1 concentrations after 48 and 72 h of exposure time, respectively. Our results provide significant information about the new antigiardial agent and proposed the nano-chitosan and emodin for the development of new drugs against G. lamblia in the future.

Ethnopharmacology of Cuscuta epithymum: A comprehensive review on ethnobotany, phytochemistry, pharmacology and toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: Cuscuta epithymum (L.) L. (C. epithymum; Convolvulaceae) is a parasitic plant that has long been used locally and traditionally in Asia, Europe and other regions. AIM OF THE REVIEW: The study intends to reflect the significance of the C. epithymum in traditional medicine. This review aims to grant insight into the species' botany, pharmacological activities and phytochemistry with distinctive emphasis on its ethnomedicinal and traditional applications in all over the world. The review endeavors to rule out any inconsistency between the species' traditional application and its pharmacological activity, and presenting any coherence existing. MATERIALS AND METHODS: The books on ethnomedicine and the main medieval Persian medicine textbooks including Makhzan Al- Advieh, The canon of medicine, Zakhireh kharazmshahi and etc were explored for C. epithymum. Additionally, information on the ethnobotany, phytochemistry, morphology, taxonomy, modern medicinal uses, and pharmacological activities were collected in electronic databases including Google Scholar, Science Direct, Scopus, and PubMed using the keywords "Cuscuta epithymum," "traditional medicine," "ethnomedicine," "phytochemistry," "pharmacology" and "activity." Then, the available articles from 1975 to 2017 were employed for this study. RESULTS: C. epithymum is a rootless plant, widely distributed and available in every continent except Antarctica. It was used traditionally in formularies or by rural people and as geriatric drug, detergent, purgative, disorders in the melancholic humor, joint, kidney, urinary tract, gastrointestinal system, nervous system, etc. In modern medicine, the extract of C. epithymum showed anti-microbial, cytotoxic, anticonvulsant, anti-urease, immune stimulatory, hepatoprotective effect, and antioxidant activity. The main phytochemical constituents are alkaloids; saponins; tannins; triterpenoids; steroids; carbohydrates; aromatic compounds; flavonoids and the hydroxycinnamic acid derivatives. CONCLUSION: The modern pharmacological studies have validated the traditional and ethnobotanical uses of C. epithymum. However, many aspects of this herb have not been studied yet. In addition, information about the phytochemistry and toxicological profile is insufficient. Owing to the extensive traditional uses of C. epithymum. Hence further studies on pharmacological activities, phytochemistry, and toxicity and adverse effects seem to be necessary to appraise the medicinal values of C. epithymum.

Comparison of Albizia Julibressin and Silver Sulfadiazine in Healing of Second and Third Degree Burns.

BACKGROUND: Large numbers of population suffer from burn annually. The promising treatment of burn has not been identified yet. Albizia julibressin (A. julibressin) in Fabaceae family is popular for its antiseptic activity. This prospective study was designed to compare the wound healing effects of A. julibressin gel (AG) with silver sulfadiazine (SSD). METHODS: This single blind clinical trial was performed on 40 patients with second and third degree burns. 20 patients treated with SSD and 20 other patients received A. julibressin. The percentage of the wound healing was evaluated with pain, irritation, edema, itching, erythema, purulent discharges and skin discoloration symptoms. Also, the patients' satisfaction and adverse drug reactions were determined. RESULTS: The severity of pain (p=0.03), inflammation (p=0.02) and purulent secretions (p=0.03) were significantly relieved in A. julibressin group. The healing time significantly reduced in second degree burns (p=0.03) and third degree burns (p=0.04) with treating by A. julibressin. No significant adverse drug reactions were detected with A. julibressin. CONCLUSION: It seems that A. julibressin improves the different therapeutic aspects of burn injuries and could be considered as a new herbal remedy in wound healings.

Genoprotective effects of Origanum vulgare ethanolic extract against cyclophosphamide-induced genotoxicity in mouse bone marrow cells.

CONTEXT: Cyclophosphamide (CP), an alkylating chemotherapeutic agent, can bind DNA, causing chromosome breaks, micronucleus (Mn) formation, and cell death. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against DNA damage. OBJECTIVE: The genoprotective effect of O. vulgare ethanolic extract against CP-induced genotoxicity in mouse bone marrow cells was evaluated using a Mn assay. MATERIALS AND METHODS: Mice were pre-treated with aerial parts of O. vulgare ethanolic extract at different doses (50, 100, 200, or 400 mg/kg) for 7 d. One hour after the last administration of O. vulgare, animals were injected with CP at 200 mg/kg. After 24 h, the bone marrow cells of both femurs were flushed and the frequency of MnPCEs was evaluated to measure the chromosomal damages. In addition, the number of PCEs per 1000 NCEs in each animal was recorded to evaluate the bone-marrow suppression; mitotic activity was calculated as [PCE/(PCE + NCE)] × 100 to assess the cell division. RESULTS: At 400 mg/kg, O. vulgare displayed its maximum protective effect, reduced the number of MnPCEs from 10.52 ± 1.07 for CP group to 2.17 ± 0.26 and completely normalized the mitotic activity (p < 0.001). Origanum vulgare also led to significant proliferation and hypercellularity of immature myeloid elements after the mice were treated with CP, mitigating the bone marrow suppression. DISCUSSION AND CONCLUSION: Origanum vulgare ethanolic extract exerts a potent genoprotective effect against CP-induced genotoxicity in mice bone marrow, which might be possibly due to the scavenging of free radicals during oxidative stress conditions.

Protective effects of Origanum vulgare ethanol extract against cyclophosphamide-induced liver toxicity in mice.

UNLABELLED: Abstract Context: Despite its wide clinical use, cyclophosphamide (CP), an alkylating chemotherapeutic agent, possesses many adverse effects, including hepatotoxicity. Because Origanum vulgare L. (Lamiaceae) has antioxidative properties, it might protect against above-mentioned damage. OBJECTIVE: This study evaluated the protective effects of O. vulgare extract on CP-induced liver toxicity. MATERIALS AND METHODS: Mice were pretreated with aerial parts of O. vulgare ethanolic extract (intraperitoneally) at doses of 50, 100, 200, and 400 mg/kg for 7 consecutive days before the administration of a single 200 mg/kg intraperitoneal dose of CP 1 h after the last injection of O. vulgare. After 24 h, animals were anesthetized, blood samples and hepatic tissues were collected and used for biochemical and histological examination. RESULTS: Serum levels of hepatic markers were increased after CP treatment but restored in the O. vulgare-pretreated groups. The serum ALT, AST, and ALP of the CP group were 196.49 ± 3.82, 143.78 ± 4.79, and 203.18 ± 3.81 IU/l, respectively. However, pretreatment with 400 mg/kg O. vulgare significantly decreased the serum ALT, AST, and ALP to 52.49 ± 2.18, 44.78 ± 2.06, and 65.62 ± 1.73 IU/l, respectively (p < 0.001). Histological examinations also confirmed the protective effects of O. vulgare against CP-induced liver toxicity. DISCUSSION AND CONCLUSION: Our results reveal that O. vulgare with high amount of flavonoids and phenolic compounds induces potent hepatoprotective mechanisms against CP. Therefore, O. vulgare might help defend the body against the side effects, particularly hepatic damages induced by chemotherapeutic agents.

Prophylactic efficacy of melatonin on cyclophosphamide-induced liver toxicity in mice.

The current study aimed to evaluate the protective effects of melatonin, a pineal secretory product, against hepatotoxicity induced by cyclophosphamide (CP) in mice. Mice were pretreated with melatonin intraperitoneally for 7 consecutive days before the administration of a single intraperitoneal dose of 200 mg/kg CP. 24 hr after CP administration, the mice were anesthetized, blood was then removed, and serum toxicity enzymes activities were evaluated. After the blood sampling, all animals were killed, livers were then removed, and histological studies were conducted. Serum toxicity marker enzymes were significantly increased after CP treatment but restored in melatonin pretreated groups. In addition, administration of CP induced necrotic hepatocyte with small crushed nuclei, portal space with severe inflammation, and hepatocytes surrounded by lymphocytic infiltration in hepatic tissues. However, melatonin effectively protected against CP-induced histopathological abnormalities in the liver tissues. Our results reveal that melatonin produces a potent hepatoprotective mechanism against CP. Therefore, melatonin could be a potent candidate to use concomitantly as a supplement agent against hepatotoxicity of CP for the patients undergoing chemotherapy.

An ethanol extract of Origanum vulgare attenuates cyclophosphamide-induced pulmonary injury and oxidative lung damage in mice.

CONTEXT: Injury to normal tissues is the major limiting side effect of using cyclophosphamide (CP), an antineoplastic alkylating compound. OBJECTIVE: This study was undertaken to evaluate the protective effect of an extract of Origanum vulgare L. (Lamiaceae), an antioxidative medicinal plant, against CP-induced oxidative lung damage in mice. MATERIALS AND METHODS: Mice were pre-treated with various doses of O. vulgare extract (50, 100, 200, and 400 mg/kg) for 7 consecutive days followed by an injection with CP (200 mg/kg b.w.) One hour after the injection of O. vulgare on the last day, mice were injected with CP; 24 h later, they were euthanized, their lungs were immediately removed, and biochemical and histological studies were conducted. RESULTS: A single dose of CP markedly altered the levels of several biomarkers associated with oxidative stress in lung homogenates. Pretreatment with O. vulgare significantly reduced the levels of lipid peroxidation and attenuated the alterations in glutathione content and superoxide dismutase activity induced by CP in lung tissue. In addition, O. vulgare effectively alleviated CP-induced histopathological changes in lung tissue. CONCLUSIONS: Our results revealed that O. vulgare protects lung tissues from CP-induced pulmonary damage and suggest a role for oxidative stress in the pathogenesis of lung disease produced by CP. Because O. vulgare has been extensively used as an additive agent and is regarded as safe, it may be used concomitantly as a supplement for reducing lung damage in patients undergoing chemotherapy.

The mitigating effect of Citrullus colocynthis (L.) fruit extract against genotoxicity induced by cyclophosphamide in mice bone marrow cells.

Possible genoprotective effect of Citrullus colocynthis (L.) (CCT) fruits extract against cyclophosphamide- (CP-)induced DNA damage in mice bone marrow cells was evaluated using micronucleus assay, as an index of induced chromosomal damage. Mice were preadministered with different doses of CCT via intraperitoneal injection for 7 consecutive days followed by injection with CP (70 mg/kg b.w.) 1 hr after the last injection of CCT. After 24 hr, mice were scarified to evaluate the frequency of micronucleated polychromatic erythrocytes (MnPCEs). In addition, the number of polychromatic erythrocytes (PCEs) among 1000 normochromatic erythrocytes (NCEs) per animal was recorded to evaluate bone marrow. Pretreatment with CCT significantly reduced the number of MnPCEs induced by CP in bone marrow cells (P < 0.0001). At 200 mg/kg, CCT had a maximum chemoprotective effect and reduced the number of MnPCEs by 6.37-fold and completely normalized the mitotic activity. CCT also led to marked proliferation and hypercellularity of immature myeloid elements after mice were treated with CP and mitigated the bone marrow suppression. Our study revealed that CCT has an antigenotoxic effect against CP-induced oxidative DNA damage in mice. Therefore, it could be used concomitantly as a supplement to protect people undergoing chemotherapy.