Avicenna Journal of Phytomedicine
Volume:11 Issue: 4, Jul-Aug 2021

Acute promyelocytic leukemia (APL) is among the most threatening hematological malignant cancers. Defects in cell growth and apoptotic pathways lead to the pathogenesis of the disease as well as its resistance to therapy; therefore, it is a good candidate for examining pro-apoptotic agents. The present study compared the molecular mechanism induced by kaempferol and epigallocatechin gallate (EGCG) as well as all-trans retinoic acid (ATRA) in HL-60 leukemia cells during five days.

Cell viability was determined by resazurin assay following treatment with ATRA (10 µM), EGCG, and kaempferol (12.5-100 µM), and apoptosis was detected by the Anx V/PI kit. Moreover, the levels of genes involved in apoptosis (PI3K, AKT, BCL2, BAX, P21, PTEN, CASP3, CASP8, and CASP9) and multi-drug resistance (ABCB1 and ABCC1) were assessed by using real-time PCR test.

Based on the findings, kaempferol decreased cell viability and increased apoptosis in HL60 cells more than EGCG. Apoptosis was induced via extrinsic and intrinsic pathways in HL60 cells by kaempferol and EGCG. In addition, kaempferol and EGCG increased apoptosis and inhibited MDR in a concentration- and time-dependent manner.

Kaempferol at high concentrations can be taken into consideration for treating patients with APL as compared with EGCG.

During recent years, evidence-based practice as a way to support higher standards of care was emphasized by health care policymakers. Sexual dysfunction (SD) is a common problem that affects the quality of life in individuals. Today, the use of Ginkgo biloba extract (GBE) for treating SD has been considered, so this study was performed to evaluate the current evidence for the efficacy and safety of ginkgo in treating SD.

In this review study, electronic databases of PubMed, Scopus, Cochrane, Google Scholar, Web of science and Persian databases such as SID and Magiran were searched up to March 2020, to identify all the studies reporting the effect of GBE for effectiveness on sexual function and its safety. The search was performed using the keywords of Ginkgo, Ginkgo biloba, Complementary and alternative medicine, women sexual dysfunction, and male sexual dysfunction. The quality of included studies was assessed using the Oxford Center for Evidence Based Medicine checklist.

Among 156 articles found in the initial search, 5 randomized controlled trials (475 participants) were selected for this study. After a meticulous review, we found that G. biloba can have positive effects on the sexual function of postmenopausal women, while evidence shows that it has no effect on the sexual function of antidepressants users. Headaches and gastrointestinal disturbance were among the adverse events mentioned in several trials.

We concluded that G. biloba has limited positive effects on sexual function and more studies are needed to confirm these findings.

Recently, saffron (Crocus sativus L. from the Iridaceae family) has been characterized by its antioxidant, anti-inflammatory and analgesic effects. This study aimed to evaluate the effect of saffron on disease activity in patients with rheumatoid arthritis (RA). This is a double-blind, placebo-controlled, randomized clinical trial (RCT) performed on 55 newly- diagnosed RA patients without previous treatment, who were randomly divided into intervention (included 28 cases) and control groups (consisted of 27 individuals). Standard therapy including prednisolone, oral methotrexate, folic acid, vitamin D, calcium, and alendronate, was administered similarly in both groups.  Patients received a 100 mg saffron pill/day (pure saffron powder) or placebo besides the standard protocol. The placebo had the same shape as the saffron pills. Follow up of DAS28ESR disease activity score was done on the 30th, 45th and 90th day of the study. There was no difference between the intervention and control groups regarding to the DAS28ESR at the end of the study. However, a significant decrease in DAS28-ESR was observed in each group compared to the first visit (p=0.001). The results also showed no significant difference in the incidence of side effects in both groups. In summary, patients who received pure saffron pills (100 mg/day) in addition to standard therapy did not have a significant difference in improvement of disease activity from the patients on standard therapy.

This study aims to shed a new light on pharmacological effects of bee bread as a product of the hive through examination of the effect of itsethyl acetate extract onhyperglycemia, dyslipidemia, and liver dysfunction induced by streptozotocin. The bee bread ethyl acetate extract was analyzed for total phenolics, flavonoids, and the antioxidant activities using total antioxidant capacity, 2, 2- diphenyl-1-picrylhydrazyl (DPPH), 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and reducing power assays. In vivo study was carried out on thirty-six rats divided into control or diabetic rats, received daily for 15 days distilled water (10 ml/kg), or ethyl acetate extract of bee bread (100 mg/kg), or glibenclamide (2.5 mg/kg). The protective effect of bee bread against metabolic changes induced by streptozotocin in Wistar rats, was evaluated by checking the blood glucose levels, lipid profile, atherogenic index, coronary risk index, cardiovascular risk index, body weight and hepatic enzyme markers in normal and diabetic rats. Glibenclamide was used as standard drug to compare the efficacy of bee bread. The results indicate that bee bread ethyl acetate extract has a high content of phenolics and flavonoids and a strong antioxidant activity. Glycemia, lipid profile and hepatic enzymes were modified in diabetic rats. These modifications were ameliorated after the treatment withbee bread extract which was more potent than glibenclamide. In summary, ethyl acetate extract of bee bread possesses effective glycemia lowering effects and representsa natural source of new bioactive molecules for future therapy of hyperglycemia, hyperlipidemia and liver dysfunction.

A fraction from Khaya grandifoliola has recently been shown to inhibit hepatitis C virus (HCV) infection and three limonoids (17-epi-methyl-6-hydroxylangolensate, 7-deacetoxy-7-oxogedunin and 7-deacetoxy-7R-hydroxygedunin) were purified from this fraction. The present study aimed at assessing the inhibitory effect of these limonoids on HCV using cell-culture derived HCV (HCVcc) system.
Cytotoxic effects of the limonoids on Huh7.5 cells were assessed by MTT assay. Huh7.5 cells were transfected with RNA transcripts of the plasmid Jc1/GLuc2a, carrying a Gaussia luciferase reporter gene to rescue the HCVcc particles which were used to infect naïve cells in the presence or absence of the studied limonoids during 72 hr. Infection and replication rates were monitored by luciferase reporter assay and immunofluorescence assay (IFA) while cellular gene expression was analyzed by western blot, respectively.
The limonoids inhibited HCV infection mostly by targeting entry and replication stage. Their inhibitory effect on entry step, comparable to that of anti-CD81 antibody, was related to the blocking of CD81 receptor. In the replication step, the limonoids decreased the expression of NS5B similar to danoprevir. These compounds also significantly decreased but up-regulated the expression of Class-III phosphatidylinositol 4-kinase alpha and 2’,5’-oligoadenylate synthase-3, respectively.
The present findings suggest that limonoids from K. grandifoliola are potential anti-HCV agents and may offer an advantage in the treatment of HCV infection.

Farnesoid-X-activated receptors (FXR) are key modulators of liver regeneration. Milk thistle and Chicory are known as potent protective remedies in several liver disorders. The objective of this work was to examine the role of FXR in the hepato-healing properties of milk thistle (MTE) and chicory extracts (CE) in a rat model of acetaminophen-induced hepatotoxicity.

Male Wistar rats were randomly divided into seven groups including control, vehicle, acetaminophen (500 mg/kg/day, oral), acetaminophen plus oral MTE 200 and 400 mg/kg/day, and acetaminophen plus oral CE 500 and 1000 /kg/day for 28 days. Liver function and histology as well as the pattern of hepatic FXR expression were assessed after 4 weeks.

Administration of acetaminophen was associated with a significant elevation of liver transaminase along with the architectural injuries. In contrast, chronic concomitant administration of both MTE and CE significantly restored the liver function and structural abnormality. The main molecular findings of the study revealed that the lower doses of both MTE and CE led to a marked upregulation of hepatic FXR expression.

Discovery of the involvement of the nuclear modulating pathways in hepatoprotective activity of the extracts, providesa new mechanistic insight which needs further investigations.

Based on anti-inflammatory effects of Aloe vera, the effect of aqueous extract of this plant on brain edema and changes in some pro-inflammatory cytokines was investigated after traumatic brain injury (TBI).
In this study, adult male Wistar rats were divided into 5 groups: Sham, TBI, vehicle (Veh), and low dose (LA) and high dose (HA) Aloe vera. The vehicle and aqueous extract of Aloe vera were injected intraperitoneally 30 min after induction of diffuse TBI by Marmarou’s method. Brain edema (brain water content), and transforming growth factor beta (TGF-β), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6) and IL-1β levels in serum and brain were measured 24 hr after TBI induction.
Increased brain edema by TBI was reduced by both LA and HA (p<0.01 and p<0.05, respectively). IL-6 increased in the brain of TBI group compared to sham, and which was inhibited by both Aloe vera doses compared to Veh (p<0.001). The differences in the IL-6 serum levels among Veh, LA and HA groups were not significant. Increases in serum and brain IL-1β levels were reduced only in the HA group (p<0.001). Although only in the brain, TNF-α level increased after trauma, but both LA and HA inhibited it in a dose-dependent manner (p<0.01 and p<0.05, respectively) . The amount of TGF-β in the brain was reduced by both doses of the extract (p<0.001).
These results indicated that Aloe vera has a neuroprotective effect induced by reducing brain edema. The probable mechanism particularly for HA is decreasing levels of pro-inflammatory cytokines such as TGF-β, TNF-α, IL-6 and IL-1β.

Bisphenol A (BPA) is an organic synthetic compound, often used in manufacturing polycarbonate plastics. Researches have shown the role of BPA as an endocrine disruptor. The present study intended to evaluate the hepatoprotective properties of naringin, an active flavanone glycoside present in many citrus fruit, against hepatotoxicity induced by BPA.

Male Wistar rats were orally treated with 50 mg/kg BPA for 30 consecutive days for induction of toxicity and 40, 80 and 160 mg/kg naringin for the same period along with BPA or alone.

This study demonstrated that BPA significantly increased serum levels of triglyceride, lactate dehydrogenase (LDH), alkaline phosphatase (ALP), lipid peroxidation, and aspartate aminotransferase (AST) and significantly reduced catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity, glutathione (GSH) and caused periportal inflammation and microvesicular steatosis in rat tissue. However, BPA did not change serum levels of high-density lipoprotein-cholesterol (HDL-C), total cholesterol, alanine aminotransferase (ALT), or low-density lipoprotein-cholesterol (LDL-C). Furthermore, the results displayed that administration of 80 and 160 mg/kg naringin improved hepatotoxicity and altered lipid peroxidation level, serum values of triglyceride and liver enzymes, and oxidative stress factors that were induced by BPA. The effect of two doses of 80 and 160 mg/kg naringin was more noticeable than that of dose 40 mg/kg.

The findings suggested the protective effects of naringin against BPA-induced hepatotoxicity via ameliorating liver histopathological alteration, suppressing oxidative stress and lipid-lowering properties.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with impaired cognitive skills and learning and memory dysfunctions.  It has been suggested that pelargonidin (PG), as an antioxidant agent, has a neuroprotective effect. PG could prevent damaging effects of amyloid-beta (Aβ) deposition. The aim of this study was to determine the chronic effect of PG on hippocampal neurons and memory processes in a rat model of AD.

Twenty-eight male adult rats were divided into sham, AD, AD+PG (5 μg, intracerebroventricular), and PG (5 μg, intracerebroventricular) groups. Intracerebroventricular (ICV) injection of Aβ peptides (6 μg) was done using stereotaxic surgery. ICV administration of PG or saline was performed daily for 28 consecutive days. Behavioral analysis was performed using the novel object recognition (NOR) and passive avoidance tests. Neuronal apoptosis was detected using TUNEL assay in the hippocampus.

The ICV injection of Aβ reduced step-through latency and discrimination index in behavioral tests (p <0.001). Aβ increased the number of apoptotic neurons (p <0.001). PG treatment decreased the time spent in the dark compartment and neuronal apoptosis in the AD+PG rats (p <0.001). PG increased the discrimination index in the NOR test (p <0.001).  Although PG did not change behavioral variables, it decreased cell death in the PG group.

PG attenuated neuronal apoptosis and improved cognition and memory deficiency in AD rats. The protective effect of PG against Aβ may be due to its anti-apoptotic property. It is suggested that PG can be useful to treat AD.

Application of vesicular drug delivery systems has made major progress in pharmaceutical science and technology. Niosomal drug delivery is potentially efficient to improve the pharmacokinetic and pharmacological properties of many compounds. Curcumin (CUR) has several documented anticancer activities; however, it has a low bioavailability that necessitates the development of efficient delivery systems. Accordingly, different niosomal preparations were prepared and evaluated in the present study to find a suitable delivery system.

Span and Tween 20, 40, 60, and 80 were employed with various concentrations of cholesterol for studying the ability to form curcumin-loaded niosomes. Multiple characterization techniques including visual evaluation, particle size analysis, stability, encapsulation efficiency (EE), and release profile were studied. Cytotoxicity of curcumin niosomes on MCF-7 and 3T3 cell lines was determined using MTT assay.

Visual and particle size analysis indicated the formation of seven niosomal formulations in the micron size range, while the formulation consisted of Tween 40/cholesterol (50/50 M%) with 0.05% w/v CUR had an average diameter of 475 nm. The latter formulation was selected and it had EE of 78.5%. The CUR release profile showed 18.7% release over a period of 300 min. The MTT results showed that CUR incorporation significantly increased the cytotoxicity of niosomes and the extent of toxicity was higher in MCF-7 cells.

In this study, a simple niosomal formulation was developed for CUR loading with favorable physicochemical properties. The presented niosomal curcumin had also considerable effects in cell toxicity studies, which can be suggested for future anticancer studies.