Rheum khorasanicum. Hydroalcoholic root extract induces cell death in human colorectal adenocarcinoma: An in vitro and in silico study.

Colorectal cancer (CRC) is the second greatest cause of cancer-related death in the world and chemotherapy, as an important part of CRC treatment, has some drawbacks, including systemic toxicity. Therefore, it is crucial to discover new and more effective CRC treatment plans. Rheum khorasanicum (R. khorasanicum) is a medicinal plant with high flavonoids, stilbenes, and anthraquinone contents, so it can be a potential source of antioxidants and can be used for therapeutic purposes and trigger apoptosis in cancer cells. In this study, we investigated the effects of hydroalcoholic root extract of R. khorasanicum treatment on inducing mitochondrial apoptosis of HT-29 and Caco-2 human colorectal adenocarcinoma cells. Firstly, the total phenolic and flavonoid content was determined. Then, the cytotoxic effects of R. khorasanicum on cells of three different types, including HT-29 and Caco-2 colon cancer cells as well as normal 3T3 cells were assessed using the MTT assay. To investigate the characteristics of cellular death, flow cytometry, and western blotting were performed. The results of this study indicated considerable phenolic (356.4±9.4 GAE/gDW) and flavonoid (934.55±17.1 QE/gDW) contents in R. khorasanicum. MTT assay's finding indicated that 100, 60, and 30µg/mL concentrations of R. khorasanicum reduce cell viability in HT-29 and Caco-2 cell lines significantly (P<0.05). It has been also revealed that R. khorasanicum extract induces apoptosis rather than necrosis in these cell lines. Moreover, Bcl-2 expression was significantly reduced in both HT-29 and Caco-2 cell lines, while Bax and cleaved caspase-3 expression soared considerably in the groups under R. khorasanicum treatment (P<0.05). In conclusion, our findings have suggested that high phenol and flavonoid contents of R. khorasanicum root extract possibly play an important role in cell cytotoxicity and apoptosis induction in HT-29 and Caco-2 colon cancer cells.

Inhalation of Spray-Dried Extract of Salvia rosmarinus Spenn Alleviates Lung Inflammatory, Oxidative, and Remodeling Changes in Asthmatic Rats.

INTRODUCTION: For centuries, Salvia rosmarinus Spenn has been applied as folk medicine to cure different diseases due to its anti-inflammatory, antibacterial, antioxidant, antifungal, and antitumor effects. To find bioactive medicinal herbs exerting a protective effect on airway inflammation and remodeling, we assessed the anti-oxidative and anti-inflammatory effects of an aqueous spray-dried extract of Salvia rosmarinus Spenn. (rosemary) in an ovalbumin-induced asthmatic rat model. METHODS: Rats were randomly divided into normal control (control), asthma, asthma+rosemary extract (RE) (13 mg/kg), asthma+RE (50 mg/kg), and asthma+budesonide groups. After 50 days, animals were anesthetized, and then blood, bronchoalveolar lavage fluid (BALF), and lung tissues were collected for subsequent serological and pathological studies. Histopathology of lung tissues was evaluated by H&E staining. The oxidative stress parameters and airway inflammation factors in BALF and lung tissue were explored. RESULTS: Using thin layer chromatography, the presence of rosmarinic acid was confirmed in aqueous extract of rosemary. Furthermore, RE markedly decreased immunoglobulin E levels (50 mg/kg; p < 0.001 vs. asthma group) and inflammatory cytokines (50 mg/kg; p < 0.001 vs. asthma group) and increased antioxidant enzymes (50 mg/kg, p < 0.001 vs. asthma group). Furthermore, RE at a concentration of 50 mg/kg obviously reduced the number of inflammatory cells, goblet cells, and pathological changes compared to the asthma group. CONCLUSION: The results showed that RE administration might prevent or alleviate allergic asthma-related pathological change, probably via antioxidant and anti-inflammatory mechanisms.

Lithium and zinc levels along with oxidative status in myocardial infarction: A case-control study.

Background: Coronary artery disease (CAD) and myocardial infarction (MI) are the most prevalent diseases globally. While several risk factors for MI are well assessed, the influence of trace elements on MI has not been thoroughly studied. This study aimed to evaluate lithium (Li) and zinc (Zn) levels in MI patients and healthy control and assess their relationship with oxidative stress (OS) parameters, such as nitric oxide (NO) and total antioxidant capacity (TAC). Methods: This case-control study was performed on 182 patients with MI and 83 healthy subjects at Shafa Hospital in Kerman, Iran. MI patients were divided into two groups based on the angiography results: those with coronary artery block above 50 % (CAB >50 %, n = 92) and those with coronary artery block below 50 % (CAB <50 %, n = 90). A flame atomic absorption spectrometer was used to detect Li and Zn levels, and biochemical indices were measured by an autoanalyzer. Also, ferric reducing antioxidant power assay and the Griess method were used to measure the amounts of NO and TAC. Results: The levels of TAC and Li were significantly higher in the control group than in the patient groups (in both CAB >50 % and CAB <50 % groups). Furthermore, in the CAB <50 % group, TAC and Li levels were significantly higher than in the CAB >50 % group. In the Zn levels evaluation, higher concentration was seen in the CAB >50 % group compared to the CAB <50 % group (P < 0.05). Moreover, Zn and NO levels were significantly higher in both CAB groups compared to controls. In continue, Li levels had a positive association with TAC and ejection fraction percentage (EF%) as well as a negative association with NO levels and Zn levels had a significant positive association with NO and a negative association with TAC. In logistic regression analysis, Li, TAC, and high-density lipoprotein-cholesterol significantly decreased the odds ratio (OR) of MI, whereas Zn, NO, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-sensitivity C-reactive protein (hs-CRP) significantly increased the OR of MI. Furthermore, the area under the curve (AUC) analysis indicated that Li had the highest AUC for the diagnosis of CAB >50 % (Li < 167 ng/mL), and Zn ≥ 1810 µg/mL increased disease severity. Conclusion: Our investigation revealed that Li had a protective effect against CAD by decreasing OS and increasing EF%. However, Zn at concentrations higher than 1810 µg/mL was found to be cytotoxic and increased the risk of MI through increased OS. Taken togather, it could be concluded that Li supplementation may decrease the risk of CAD.

Efficacy of frankincense-based herbal product in urinary incontinence: A randomized, double-blind, placebo- and active-controlled clinical trial.

Urinary incontinence is a silent epidemic that has a serious impact on a person's quality of life (QOL). This study aimed to evaluate the efficacy of frankincense-based herbal product (FHP) in urinary incontinence compared with placebo and solifenacin. In this randomized, double-blind clinical trial, 120 postmenopausal women with mixed urinary incontinence were randomized to one of the three groups of FHP, placebo, and standard treatment (solifenacin). Frequency, amount of leakage, and score of urinary incontinence as well as the QOL were measured at the end of the second and fourth weeks and 2 weeks after the interruption of the treatment. The ICIQ-UI SF and I-QOL questionnaires were used for the measurements. Mean frequency of urinary incontinence and amount of leakage significantly decreased in the FHP and solifenacin groups in the fourth week compared to the placebo group. In addition, 2 weeks after treatment completion, the effects of the FHP were significant compared to the solifenacin group. Due to the effect of FHP on improving the QOL and also the prolonged effect of this drug, the use of FHP in urinary incontinence, as a complementary treatment could be suggested.

Effects of the Ethanol and Ethyl Acetate Extracts of Terminalia chebula Retz. on Proliferation, Migration, and HIF-1α and CXCR-4 Expression in MCF-7 Cells: an In Vitro Study.

Over recent years, much attention has been devoted to the field of screening natural products and/or their novel structures because of reversing cancer progression. The current research work was intended to explore the cytotoxic activity of ethanol and ethyl acetate extracts of dried fruit of Terminalia chebula Retz. (T. chebula) in MCF-7 cell line. High-performance thin-layer chromatographic (HPTLC) method and Folin-Ciocalteu colorimetric techniques were performed. Anti-proliferative activities of T. chebula fruit extracts on the MCF-7 cell line were evaluated using MTT assay. Effects of both extracts on the migration of MCF-7 cells and the size of MCF-7-derived spheroids were also evaluated. Moreover, antioxidant properties were measured by DPPH and FRAP methods. Western blotting was used to measure the HIF-1α and CXCR-4 protein levels. Chebulagic acid, gallic acid, chebulinic acid, and ellagic acid were found as major compounds in both extracts. The total phenolic contents based on gallic acid equivalent (GAE) in the ethanol and ethyl acetate extracts of T. chebula were found to be 453.68 ± 0.31 and 495.12 ± 0.43 mg GAE/g dry weight of the extract, respectively. Both extracts exerted a significant dose- and time-dependent cytotoxicity effect on MCF-7 cells. They also had a marked negative effect on the average size of MCF-7-derived spheroids and their migration rate. None of the extracts exhibited stronger antioxidant activities than vitamin C. Furthermore, both extracts at a concentration of 125 µg/ml could meaningfully decrease the expression levels of HIF-1α and CXCR-4 in MCF-7 cells. These data represent that T. chebula may be a valuable medicinal resource in the regulation of breast cancer proliferation, growth, and metastasis.

Herbal therapy in opioid withdrawal syndrome: A systematic review of randomized clinical trials.

Background: Medicinal plants have revealed much attention as an alternative or complementary treatment for opioid withdrawal syndrome. The current review collects all available literature to verify the efficiency of herbal remedies in the management of symptoms associated with opioid withdrawal. Methods: A systematic literature search was conducted from January 1990 to May 2021 on four bibliographic databases (Scopus, PubMed, Embase, and Web of Science) using the search terms "medicinal plant", "withdrawal syndrome", "opioid", and all their equivalents. All randomized controlled trials (RCTs), published in the English language were included for data synthesis. The search was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). The Cochrane risk of bias tool was used to verify the quality of the included clinical trials. Findings: A total of 12 RCTs were collected and used for data synthesis. The results of these studies indicated that herbal medicines were effective in treating opioid withdrawal syndrome and could alleviate the withdrawal symptoms, such as abdominal constrictions, diarrhea, bone pain, perspiration, and insomnia, when compared to conventional medications such as buprenorphine, clonidine, and methadone. However, more than 30% of RCTs were found to be at high risk of bias in the areas of selection, performance, detection, attrition, and reporting. Conclusion: Although several RCTs have proven that herbal remedies are effective in reducing opioid withdrawal symptoms, the findings need to be viewed more carefully. Further RCTs with more participants, longer duration, and less risk of bias are needed in the claimed cases.

Effect of an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. on oxidative stress, memory impairment and withdrawal syndrome induced by morphine.

Background: Traditional Persian medicine has introduced effective remedies in opioid dependence care. One of the most widely used remedies is an herbal formulation containing Peganum harmala L. and Fraxinus excelsior L. (HF). This study investigated the effects of HF to attenuate the withdrawal signs and rewarding effects in morphine-dependent rats.Methods: Forty-nine male Wistar rats were randomly divided into seven groups. The control and vehicle groups received normal saline and sodium carboxymethyl cellulose, respectively. The morphine group received morphine for one week. The single and daily dose of HF groups received morphine similar to the morphine group, and HF (1.4 and 2.8 g/kg) once a day in the daily dose group and only on the last day of the experiment in the single dose of HF group. Finally, the withdrawal signs as well biochemical tests were evaluated. The behavioral parameters were assessed by conditioned place preference (CPP), elevated plus-maze and Y-maze tests. The antioxidant activity of HF was evaluated by measurement of serum contents of malondialdehyde, stable nitric oxide metabolites and total antioxidant capacity (TAC). Moreover, the protein expression of c-fos was assessed by western blotting.Results: Daily treatment with HF significantly reduced the score of CPP behavioral test, all of the withdrawal signs, TAC and the c-fos protein level.Conclusions: The results indicated that HF might be a promising complementary treatment in reducing morphine-induced physical and psychological dependence probably through modulation of c-fos protein expression.

Iron Chelator or Iron Supplement Consumption in COVID-19? The Role of Iron with Severity Infection.

Iron is a trace element that is used to replicate the virus and has a role in the vital functions of the body and the host's innate immune system. The mechanism of iron in COVID-19 severity is still not well understood. The aim of this study was to evaluate the association of the iron with COVID-19 severity. A case-control study was performed on 147 patients with a positive PCR test result and 39 normal individuals admitted to the Persian Gulf Martyrs Hospital in Bushehr, Iran. The iron profiles and related tests were measured along with hematological analytes. Hemoglobin (Hb), Fe, and saturated transferrin decreased in all the groups compared to the controls, but ferritin increased in the patient groups. After adjusting for age and sex, we found that increased ferritin levels augmented the odds ratio (OR) of the disease in the moderate (OR = 2.95, P = 0.007), severe (OR = 6.1, P < 0.001), and critical groups (OR = 8.34, P < 0.001). The decreased levels of Fe reduced the OR of the disease in the mild (OR = 0.96, P < 0.001), moderate (OR = 0.96, P < 0.001), severe (OR = 0.95, P < 0.001), and critical (OR = 0.98, P = 0.001) groups. Fe (AUC = 85.95, cutoff < 75.5 µg/dL, P < 0.001) and ferritin (AUC = 84.45, cutoff > 157.5 ng/dL, P < 0.001) have higher AUC for disease prognosis, but only ferritin (AUC = 74.89, cutoff > 261.5 ng/dL, P < 0.001) has higher AUC for disease severity assays. It could be concluded that the use of iron chelators to reduce iron intake can be considered a therapeutic goal. In addition, measuring Fe and ferritin is beneficial for the diagnosis of the disease and determining its severity.

Phytosomes as Innovative Delivery Systems for Phytochemicals: A Comprehensive Review of Literature.

Nowadays, medicinal herbs and their phytochemicals have emerged as a great therapeutic option for many disorders. However, poor bioavailability and selectivity might limit their clinical application. Therefore, bioavailability is considered a notable challenge to improve bio-efficacy in transporting dietary phytochemicals. Different methods have been proposed for generating effective carrier systems to enhance the bioavailability of phytochemicals. Among them, nano-vesicles have been introduced as promising candidates for the delivery of insoluble phytochemicals. Due to the easy preparation of the bilayer vesicles and their adaptability, they have been widely used and approved by the scientific literature. The first part of the review is focused on introducing phytosome technology as well as its applications, with emphasis on principles of formulations and characterization. The second part provides a wide overview of biological activities of commercial and non-commercial phytosomes, divided by systems and related pathologies. These results confirm the greater effectiveness of phytosomes, both in terms of biological activity or reduced dosage, highlighting curcumin and silymarin as the most formulated compounds. Finally, we describe the promising clinical and experimental findings regarding the applications of phytosomes. The conclusion of this study encourages the researchers to transfer their knowledge from laboratories to market, for a further development of these products.

The efficacy of a traditional medicine preparation on second-degree burn wounds in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Lime Salve (L.S) has been well documented from the 9th to the 19th century AD by traditional Iranian medicine (TIM) as an effective remedy for burn healing. AIM OF THE STUDY: The present study was undertaken to evaluate the healing effect and related underlying mechanisms of Lime Salve in a model of deep second-degree thermal burn in male Wistar rats. MATERIALS AND METHOD: L.S was made up of a combination of refined calcium hydroxide powder, beeswax and sesame oil and its quality control was assessed. A deep second-degree burn was created by a hot plate in 48 male Wistar rats. Afterwards, they were randomly divided into four groups including normal saline (C group), L.S (T group), basement of formulation composed of beeswax and sesame oil (B group) and silver sulfadiazine (S group). On days 5, 10, 17 and 24, the wounds were digitally photographed by a camera and after sacrifice of the rats, skin samples were obtained for performing qRT-PCR, immunohistochemistry staining and histological examination. RESULTS: L.S prominently augmented the wound closure rate, neovascularization on day 10 and collagen formation on days 17 and 24 in comparison with the C group. Furthermore, the Salve-exposed specimens showed a significant higher epithelialization during the experiment with a peak on day 24. qRT-PCR also showed that on day 10, VEGF and TGF-ß1 genes were significantly higher in the T group as compared with the C group. Also, MMP-9 and MMP-2 genes had a significant peak of expression on day 17 and rapid reduction of expression on day 24. Expression levels of IL-6 and TNF-α genes peaked on day 10 in the T group, followed by a progressive reduction until the end of the examination. CONCLUSION: L.S could effectively accelerate the healing process of deep second-degree burn wounds and therefore, it may be recommended as a promising topical medication for treating burn wounds in the future clinical trials.

Proliferation and In Vitro Wound Healing Effects of the Microniosomes Containing Narcissus tazetta L. Bulb Extract on Primary Human Fibroblasts (HDFs).

PURPOSE: In Traditional Persian Medicine (TPM), different natural treatments have been suggested for skin damages such as Narcissus tazetta L. bulb application. New drug delivery systems such as niosomes have shown considerable increase transdermal drug delivery through stratum corneum, the main barrier against substances transport into skin. The aim of this study is preparation of niosomal formulations from N. tazetta bulb extract and evaluation of its in vitro wound healing effect. MATERIALS AND METHODS: Non-ionic surfactant vesicles (NSVs or niosomes) were prepared by film hydration method from percolated extract of N. tazetta bulb. A number of 12 niosomal formulations (F1-F12) were prepared using different proportions of Span 60/Tween 60/cholesterol and 80% methanol-dissolved/aqueous PEN (percolation extract of N. tazetta) (30 and 50 mg/ml). Their morphology, particle size, physical and chemical stability and encapsulation efficiency was studied. In vitro wound healing effect of various concentrations of the best PEN niosomal formulation (F9) was evaluated in comparison to PEN on human dermal fibroblasts (HDFs). RESULTS: Increasing the aqueous/methanolic PEN concentration from 3 to 5% resulted size reduction of NSVs with statistically significant difference (p < 0.05). F9 showed the most physicochemical stability and was chosen for in vitro wound healing effect. This formulation exhibited significantly effects (p < 0.05) on cell proliferation in HDF cells at 1.562 and 3.125 µg/ml compared with the untreated cells using neutral red assay. CONCLUSION: Formulation of PEN in niosome carrier significantly decreased the gap width on human dermal fibroblasts. Graphical abstract Schematic processes of proliferation effect of narcisus tazetta bulb on fibroblast cells.

Protective effect of Berberis vulgaris fruit extract against Paraquat-induced pulmonary fibrosis in rats.

BACKGROUND: Pulmonary fibrosis induced by paraquat (PQ) has caused a large number of human fatalities all over the world, especially in Asian region. The main potential mechanism of PQ toxicity has been thought to be mediated by ROS. The present study was designed to evaluate the efficacy of the Berberis vulgaris fruit extract (BVFE) against PQ-induced pulmonary fibrosis in rats. METHODS: Forty male rats were randomly divided into five experimental groups each containing eight rats. Groups 1 and 2, served as a negative and positive control and received a single dose of intratracheal instillation of saline and PQ (20mg/kg), respectively. Groups 3-5 were treated with different doses of BVFE (100, 200, 400mg/kg/day, orally) 1 week before the PQ injection and continued for 3 weeks. The rats were sacrificed 21days after PQ. Malondialdehyde (MDA), Hydroxyproline, inflammatory and fibrogenic cytokine tumor necrosis factor (TNF)-α, interleukin (IL)-6 and transforming growth factor (TGF)-ß1 in lung tissue were determined. Presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in lung were evaluated microscopically by hematoxylin and eosin (H&E) staining. Dried extract was standardized by amount of berberine by HPTLC methods by silica gel plate. RESULTS: The results showed that PQ could significantly increase the lung MDA, hydroxyproline, TNF-α, IL-6 and TGF-ß1 levels. BVFE ameliorated the biochemical and histological lung alterations induced by PQ. CONCLUSIONS: The present study indicates the hydroalcolic extract of Berberis vulgaris fruit has beneficial effects in rat pulmonary fibrosis induced by PQ in a dose-dependent manner, possibly by anti-oxidant and anti- inflammatory properties, which might be due to its berberine alkaloid content.

Accelerated Burn Wound Closure in Mice with a New Formula Based on Traditional Medicine.

BACKGROUND: A combination of the oils of sesame, hemp, wild pistachio, and walnut has been used for treatment of skin disorders, including wound burns, in some parts of Kerman, Iran. Evaluation of this remedy in the form of a pharmaceutical formulation in animal models can pave the way for its future application in wound burn healing in humans. OBJECTIVES: This experimental study investigated the healing potential of a new formula (NF) based on folk medicine from Iran for the treatment of third degree burns in mice. The formula was a combination of the oils of four plants: sesame (Sesamum indicum L.), wild pistachio (Pistacia atlantica Desf.), hemp (Cannabis sativa L.), and walnut (Juglans regia L.). METHODS: Twenty-four mice were selected based on simple random sampling. Twenty-five percent of the total body surface area was burned by exposure to boiling water, according to the Walker-Mason method. NF and silver sulfadiazine (the positive control) were applied topically twice a day for 21 days. The burned area in the negative control group was left untreated. Epithelialization time and the percent of wound contraction were measured during the treatment period. The process of wound repairing was evaluated using histological (H and E and trichrome staining) and immunohistological (anti-pancytokeratin) methods. RESULTS: When compared to the controls, NF significantly improved wound contraction after day 10. Epithelialization time in the NF group was significantly faster than in the other groups (20 vs. 25.5 days) (P < 0.001). Histopathological and immunohistochemical findings confirmed the efficacy of the NF. CONCLUSIONS: A new therapeutic remedy was introduced for the treatment of burn wounds. Further clinical and molecular studies are suggested to determine the exact mechanism(s) involved in the burn wound healing effect of NF.

The efficacy of whey associated with dodder seed extract on moderate-to-severe atopic dermatitis in adults: A randomized, double-blind, placebo-controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis is a common chronic inflammatory skin condition that is on the rise and adversely affects quality of life of the affected individual. Dry skin and pruritus, major characteristics of this disease, are associated with the dysfunction of the skin barrier. Though mild cases of the disease can be controlled with antihistamines and topical corticosteroids, moderate-to-severe cases often require treatment with immunomodulatory drugs, which have many side effects. It is now more common to use complementary and alternative medicines in the treatment of atopic dermatitis. In traditional Iranian medicine, the use of whey with the aqueous extract of field dodder (Cuscuta campestris Yunck.) seeds in severe and refractory cases of atopic dermatitis is common and has no side effects. The aim of this study was to assess the efficacy and safety of whey associated with dodder seed extract in the treatment of moderate-to-severe atopic dermatitis in adults. MATERIALS AND METHODS: The study was a randomized, double-blind placebo control trial that was conducted on 52 patients with moderate-to-severe atopic dermatitis for 30 days. In this study patients received freeze dried whey powder with spray dried water extract of field dodder or the placebo for 15 days. At baseline (week zero), after the end of the 15 day treatment period (week three) and 15 days after stopping the drug or placebo (follow-up/week five), patients were evaluated in terms of skin moisture, elasticity, pigmentation, surface pH and sebum content on the forearm with Multi Skin Test Center® MC1000 (Courage & Khazaka, Germany) and the degree of pruritus and sleep disturbance in patients were also recorded. RESULTS: 42 patients completed 30 days of treatment with the medicine and the follow-up period. At the end of the follow-up period a significant increase in skin moisture and elasticity in the group receiving whey with dodder was observed compared with the placebo group (p<0.001). There was a significant difference between the two groups regarding the pruritus after 15 days of receiving treatment or the placebo (p<0.05), and at the end of the 30-day study period the difference was clearly significant (p<0.001). Sleep disturbance showed significant changes at the end of follow-up period (p<0.05). There was no significant difference between the two groups concerning changes in skin pigmentation, however, a significant decrease was observed in the group receiving whey associated with dodder seed extract over time (p<0.001). There were no significant alterations in skin surface pH and the amount of sebum between the two groups. Temporary side effects were reported including anorexia and mild gastrointestinal problems in drug use. It is noteworthy that in this study despite the fact that patients received whey with dodder for just 15 days, moisture and elasticity of the skin continued to increase in the second half of the study (follow-up period). This shows that the effect of whey with dodder is not transient and this drug really helped skin barrier reconstruction and accelerated the healing process of skin. This positively influenced the skin parameters and consequently the improvement of pruritus and sleep disturbance. CONCLUSIONS: The results indicate that whey associated with dodder seed extract can serve as a promising alternative for the treatment of moderate-to-severe atopic dermatitis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT2013121415790N1.