Wound repair is noticeably prolonged in a diabetic state due to a faulty inflammatory process and an underlying neuropathy. Several medicinal plants and their products have been of prime importance for the management of wounds over the years. Various mechanisms whereby medicinal plants elicit their action in wound repair are revealed and some plants are proven to be experimentally effective in enhancing wound closure and achieving healing. The mechanisms identified include hyperglycemic control, alleviation of physiological inflammation, controlled oxidative stress, infection control, and influence on gene expression. Information in this review was sourced from research and review articles in electronic databases such as Web of Science, Scopus, PubMed, and Google Scholar.

Objective: To assess the effect of oral treatment of methanolic extract of the aerial parts of Astragalus adscendens in streptozotocin-induced diabetic rats. Methods: In order to induce diabetes, rats intraperitoneally received streptozotocin at 65 mg/kg. Sixty adult male Wistar rats were allocated into six groups (10 rats per each) including the healthy control group, the diabetic group as well as the diabetic group treated with Astragalus adscendens methanolic extract at 50, 100, and 200 mg/kg per day or glibenclamide (0.6 mg/kg/day) for 28 d. The effects of Astragalus adscendens methanolic extract on the levels of glucose, insulin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, urea, uric acid, total protein, albumin, triglyceride, cholesterol, α-amylase, oxidant/antioxidant enzymes, and inflammatory cytokines were evaluated. Real time-PCR was also used for measuring the gene expression of caspase-3, Bcl2, and Bax. Results: The levels of glucose, cholesterol, triglyceride, creatinine, urea, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, and malondialdehyde considerably declined (P<0.001) in diabetic rats after treatment with Astragalus adscendens methanolic extract especially at a dose of 200 mg/kg. In addition, treatment with Astragalus adscendens methanolic extract noticeably increased the level of insulin, total protein, and albumin as well as improved the activities of catalase, glutathione peroxidase, and superoxide dismutase, as well as the expression levels of TNF-α, IL-1β, caspase-3, Bcl2 and Bax (P<0.001) compared to the diabetic control group. The extract also inhibited α-amylase in a dose-dependent manner with an IC₅₀ value of 19.6 µg/mL. Conclusions: Astragalus adscendens methanolic extract shows potent antidiabetic, anti-inflammatory, anti-apoptotic, and antioxidant effects in diabetic rats. However, more studies are needed to verify the underlying mechanism of the effect of this plant extract and test its efficacy in clinical trials.

Objective: To green synthesize and characterize copper nanoparticles (CuNPs) using Astragalus sinicus, as well as evaluate the acaricidal, larvacidal, and repellent activities of CuNPs against Hyalomma anatolicum ( H. anatolicum), one of the most prevalent ticks infesting cattle in Saudi Arabia. Methods: CuNPs were green synthesized by adding the Astragalus sinicus extract to a copper sulfate solution. The acaricidal, larvicidal, and repellent activities of CuNPs against H. anatolicum were assessed via the adult immersion test, the larval packet test, and the vertical movement behavior of tick larvae, respectively. The effects of CuNPs on acetylcholinesterase as well as oxidative enzyme activities were examined. Results: The green synthesized CuNPs displayed a spherical form with a size range of 15-75 nm. After exposure of adult H. anatolicum to different concentrations of CuNPs, the viability rate of adult H. anatolicum and the mean number, weight, and hatchability of eggs were noticeably reduced, in comparison to the control group (P<0.001). In addition, the viability rate of larvae considerably declined (P<0.001) with the LC₅₀ and LC₉₀ values of 11.30 and 20.34 µg/mL, respectively. The maximum repellent activity of CuNPs was observed at 50, 100, and 200 µg/mL with complete repellent activity after 60, 120, and 180 min of exposure, respectively. CuNPs, mainly at ½LC₅₀ and LC₅₀ concentrations, markedly suppressed the acetylcholinesterase activity of the larval stage of H. anatolicum (P<0.001). Moreover, CuNPs, mainly at LC₅₀ dose, significantly elevated malondialdehyde level while declining glutathione-S-transferase level in H. anatolicum larvae (P<0.001). Conclusions: CuNPs show potent acaricidal, larvicidal, and repellent activities against adults and larvae of H. anatolicum. However, further studies must be performed to clarify the precise mechanisms and the efficacy of CuNPs in practical use.

Objective: To evaluate the effects of ethanol extract from Ardisia gigantifolia leaves on cell proliferation and cancer stem cell (CSC) number in gastric cancer. Methods: The inhibitory effect of Ardisia gigantifolia extract on the proliferation of MKN45 and MKN74 gastric cancer cells was assessed using 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay. Non-adherent culture (3D) model was used to evaluate the effect of the extract on tumorsphere size and number. Moreover, the expression of CD44, ALDH, and p21 was determined by immunofluorescence analysis. Flow cytometric analysis was performed to evaluate cell cycle arrest and the expression of gastric CSC markers CD44 and ALDH. Real-time PCR analysis was also carried out to assess the effect of the extract on the expression of cell cycle-regulated genes. Results: Ardisia gigantifolia extract effectively inhibited cell proliferation with an IC₅₀ of 55.7 µg/mL in MKN45 cells and 123.6 µg/mL in MKN74 cells. The extract also arrested cell cycle in the G₀/G₁ phase as well as significantly reduced the size and number of tumorspheres. The markedly increased expression of p21 was observed at both mRNA and protein levels in the extract-treated adherent cells and tumorspheres. In addition, Ardisia gigantifolia extract significantly reduced the number of CD44- and/or ALDH-expressing gastric CSC. Conclusions: The development of gastric CSC can be inhibited by the ethanol extract of Ardisia gigantifolia.

Objective: To evaluate the effect of chaetocin on pyroptosis of gastric cancer cells and its underlying mechanisms. Methods: The proliferation of gastric cancer cells was detected by trypan blue staining. Flow cytometry and Hoechst/propidium iodide double staining were used to detect apoptosis and pyroptosis. Cellular ultrastructure was observed by transmission electron microscopy. The levels of p-mixed lineage kinase domain-like (MLKL), gasdermin-D (GSDMD), gasdermin E (GSDME), N-GSDMD, and N-GSDME proteins were detected by Western blotting. In addition, lactate dehydrogenase (LDH) release assay was used to verify pyroptosis induced by chaetocin, and caspase 3 inhibition test and siRNA interference test were conducted to investigate pyroptosis mechanisms. Results: Chaetocin at concentrations of 200 nmol/L to 600 nmol/L inhibited the proliferation of AGS, HGC27, MKN28, and SGC7901 gastric cancer cells in a dose-dependent and time-dependent manner by inducing apoptosis and pyroptosis. Significant ultrastructure changes, such as chromatin condensation, vacuolization, disrupted mitochondrial cristae, and increased nuclear occupancy, were observed after treatment with chaetocin in SGC7901 cells. Chaetocin at a concentration of 400 nmol/L significantly increased the number of pyroptotic cells, LDH release, and the ratio of N-GSDME/GSDME (P<0.01), which were reversed by Z-DEVD-FMK. In addition, chaetocin did not affect the expression of GSDMD. G9a silencing abolished the effect of chaetocin on the expression levels of GSDME and N-GSDME and LDH release (P&gt;0.05). Conclusions: In addition to inducing apoptosis, chaetocin inhibits gastric cancer cells by inducing pyroptosis via the caspase 3/GSDME pathway. G9a was the target of chaetocin to induce pyroptosis of gastric cancer cells.