Over the past decades, epidemiological studies have concluded that a diet rich in plant-derived products plays a pivotal role in human health. Fisetin (3,3’,4’,7-tetrahydroxyflavone) is a hydrophobic polyphenolic compound primarily found in edible plants (e.g. strawberry, blueberry, apple, grape, persimmon, kiwi, and cucumber). Various preclinical studies have revealed that fisetin exhibits a wide range of pharmacological effects such as antioxidant, anti-inflammatory, anti-carcinogenic, anti-osteoporotic, antimicrobial, and anti-diabetic properties. Therefore, the pharmacological in vitro and in vivo studies on fisetin are discussed in this review. Additionally, this review would be useful for further study regarding the potential of natural products, notably fisetin, and its therapeutic potential for the prevention and treatment of diseases.

Objective: To evaluate the potential therapeutic effect of Sang-Yod rice bran hydrolysates (SRH) and in combination with lisinopril against hypertension, endothelial dysfunction, vascular remodeling, and oxidative stress in rats with nitric oxide deficiency-induced hypertension. Methods: Hypertension was induced in male Sprague-Dawley rats by administration of a nitric oxide synthase inhibitor, N^ω- nitro-L-arginine methyl ester (L-NAME) in drinking water for 6 weeks. Hypertensive rats were administered daily with SRH (500 mg/kg/day), lisinopril (1 mg/kg/day), or the combination of SRH and lisinopril by gastric lavage for the last 3 weeks of L-NAME treatment. Hemodynamic status, vascular reactivity to vasoactive agents, and vascular remodeling were assessed. Blood and aortic tissues were collected for measurements of oxidative stress markers, plasma angiotensin-converting enzyme (ACE) activity, plasma angiotensin II, and protein expression. Results: L-NAME induced remarkable hypertension and severe oxidative stress, and altered contents of smooth muscle cells, elastin, and collagen of the aortic wall. SRH or lisinopril alone reduced blood pressure, restored endothelial function, decreased plasma ACEs and angiotensin II levels, alleviated oxidant markers and glutathione redox status, and restored the vascular structure. The effects were associated with increased expression of endothelial nitric oxide synthase and decreased expression of gp91^phox and AT₁R expression. The combination of SRH and lisinopril was more effective than monotherapy. Conclusions: SRH alone or in combination with lisinopril exert an antihypertensive effect and improve endothelial function and vascular remodeling through reducing oxidative stress and suppressing elevated renin-angiotensin system.

Objective: To evaluate the immunostimulatory potential of cross-reactive molecule heat shock protein 60 (HSP60) of filarial parasite Brugia malayi and Leishmania donovani. Methods: HSP60 of Brugia malayi (BmHSP60) was amplified using gene-specific primer, cloned in pTriEx4 vector, expressed in BL21-DE3 cells, and recombinant HSP60 (rHSP60) of ~65 kDa was purified by affinity chromatography using Ni-NTA column. The recombinant protein was desalted by the dialysis membrane, and the presence of endotoxin level was determined by Limulus amebocyte lysate assay. The recombinant protein was tested for cell proliferation, nitric oxide release, expression of Th1 and Th2 cytokines, and transcription factors (STATs) in vitro using murine macrophage cell line (J774A.1). Results: Higher cell proliferation indicated that BmHSP60 had immunostimulatory potential. rBmHSP60 exposure upregulated the expression of iNOS, STAT1, STAT4, Th1 cytokines (IFN–γ, TNF–α, IL-12), and nitric oxide release. In addition, no remarkable change was observed in the expression of IL-6, IL-10, and STAT3 in macrophage cell line J774A.1. The ELISA analysis showed the levels of IFN-γ, TNF-α, and IL-12 were upregulated while IL-10 level was downregulated, revealing that BmHSP60 triggered a Th1 immune response. Conclusions: Our study demonstrates that rBmHSP60 has immunogenic properties which effectively enhances the Th1 type immune responses, and can be used as an immunoprophylactic agent against leishmaniasis. Furthermore, in vivo studies are in progress to determine the protective role of rBmHSP60 against Leishmania donovani infection in a mouse model.

Objective: To identify the active ingredients, potential targets, and mechanism of Rhizoma coptidis by bioinformatics method, and to explore the hypoglycemic effect of Rhizoma coptidis by in vitro experiments. Methods: The chemical components of Rhizoma coptidis were collected through database search, and oral bioavailability and drug-likeness were used for preliminary screening. The targets of Rhizoma coptidis and diabetes-related targets were collected by database retrieval and reverse docking techniques, and the biological process of cross-set proteins was analyzed. The inhibitory effects of Rhizoma coptidis on α-glucosidase, α-amylase activity, and advanced glycation end products (AGEs) were determined via in vitro experiments. In addition, the effects of Rhizoma coptidis on pre-adipocyte differentiation, absorption of glucose by adipocytes, and the level of intracellular triglyceride were investigated using the adipocyte differentiation model. Results: There were 11 potentially active ingredients in Rhizoma coptidis. IL-6, caspase-3, epidermal growth factor receptor (EGFR), MYC, and estrogen receptor 1 were considered as the key genes. The bioinformatics analysis showed that Rhizoma coptidis played an anti-diabetic role mainly via biological processes and signaling pathways including hormone receptor activity, glutathione binding, steroid binding, etc. In vitro experiments showed that the extract of Rhizoma coptidis inhibited the activities of α-glucosidase and α-amylase, and the generation of AGEs; meanwhile, the extract promoted the absorption of glucose by adipocytes. In addition, the extract of Rhizoma coptidis decreased triglyceride level. Conclusions: Our network pharmacology and in vitro experiments demonstrate the anti-diabetic effects and possible underlying mechanisms of Rhizoma coptidis extract.

Objective: To determine the effect of climatic and environmental factors on the incidence of cutaneous leishmaniasis in Qom province in 2018. Methods: In this cross-sectional study, the data on cutaneous leishmaniasis incidence were collected from the Disease Control and Prevention Center in Qom province. Climatic and environmental data including Normalized Difference Vegetation Index (NDVI), Land Surface Temperature (LST), and soil moisture were extracted using satellite images. Data of altitude and sunny hours were provided based on shuttle radar topography mission digital elevation model and hemispherical viewshed algorithm, respectively. The associations of climatic and environmental variables with the incidence of the disease were analyzed by Pearson correlation method. The ArcGIS 10.3 software was used to determine the geographical distribution of these factors. Results: There were positive correlations between cutaneous leishmaniasis incidence and the two climatic factors: LST and sunny hours per day (P=0.041, P=0.016), and it had weak negative correlations with the digital elevation model (P=0.27), soil moisture (P=0.54), and NDVI (P=0.62). The time delay analysis showed that in one-, two-, and three month periods, the correlations increased with a 95% confidence interval. Accordingly, the correlation with the three-month time delay was positive and relatively strong between the cutaneous leishmaniasis incidence and LST and sunny hours (P=0.027, P=0.02); nevertheless, there were negative correlations between the cutaneous leishmaniasis incidence and the soil moisture (P=0.27) and NDVI (P=0.62). Conclusions: As Qom is located in one of the semi-arid climate zones, topography and solar energy are important factors affecting the incidence of cutaneous leishmaniasis in autumn. Therefore, appropriate disease control programs are recommended.