Terpenes are a structurally diverse family of secondary metabolites found mostly in plants and microorganisms. Beta-caryophyllene and d-limonene are abundant in aromatic medicinal plants. Beta- caryophyllene can be sourced from clove and cannabis amongst others, and d-limonene is abundant in the Citrus genera. Apart from their use in agriculture, cosmetics, and food industries, these terpenes possess a wide range of therapeutic activities, including antimicrobial, analgesic, and anticancer activities. This review discusses the anticancer effects of these two compounds against malignant tumors including breast, lung, gastrointestinal, bone, blood, endometrial, and bladder cancer. Beta-caryophyllene induces apoptosis and prevents proliferation and metastasis through the downregulation of HSP60, HTRA, survivin, XIAP, Bcl-xL, and Bcl-2 and the upregulation of caspase 3, annexin V, p21, Bad, Bak, and Bax. The anticancer activity is also mediated by G1/M arrest, ROS induction, and JAK1/STAT activation. d-Limonene exerts its anticancer effects by upregulating autophagy-linked genes, Bax, and caspase 3 and downregulating cyclin D1 and Bcl-2. These compounds also elicit synergistic effects upon co-administration with anticancer drugs and show great prospects as useful agents in the fight against cancer.
Objective: To investigate the effect of apigenin on carbon tetrachloride (CCl4)-induced liver fibrosis and elucidate the underlying mechanisms.
Methods: A mouse model of CCl4-induced liver fibrosis was used to evaluate the effects of apigenin. Liver function was assessed using biochemical tests, and inflammation-associated markers, including interleukin-1 beta (IL-1β), IL-6, IL-10, and tumor necrosis factor- alpha (TNF-α), were determined by enzyme-linked immunosorbent assay (ELISA). H&E staining, Sirius Red staining, and collagen immunohistochemistry were also conducted. In addition, antioxidant enzyme activity and the underlying mechanisms of hepatoprotective effects of apigenin were examined.
Results: CCl4 administration induced hepatic stellate cell activation and liver fibrogenesis in mice. Apigenin treatment markedly decreased liver injury markers, inflammation, oxidative stress, and collagen deposition, mitigating CCl4-induced liver fibrosis. Furthermore, it significantly suppressed the activation of the phosphoinositide 3-kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K/AKT/GSK3β) pathway by reducing the ratios of p-PI3K/PI3K, p-AKT/AKT, and p-GSK3β/GSK3β in liver tissue.
Conclusions: Apigenin ameliorates CCl4-induced liver fibrosis in mice, likely through the inhibition of the PI3K/AKT/GSK3β signaling pathway. These findings suggest that apigenin may have therapeutic potential for treating liver fibrosis.
Objective: To investigate the effects of quercetin on inflammatory signaling pathways and hepatic oxidative injury using a streptozotocin-induced liver injury model.
Methods: Four groups of 32 rats were used in this study: three groups were given streptozotocin to induce diabetes, and one group was given a normal control. For treatment groups, each group received either metformin (200 mg/kg body weight) or quercetin (50 mg/kg body weight) for a month. The expression of SREBP1c was detected by quantitative RT-PCR and fibrosis-related proteins (TGF-β and p-Smad3) was evaluated by Western blot. Furthermore, MCP and IL-1β were determined by ELISA.
Results: Quercetin significantly reduced insulin and glucose levels. Besides, it reduced the serum levels of ALT, AST, and ALP, improved lipid profile, lowered the MDA level, increased SOD activity, decreased the rise in MCP-1 and IL-1β, inhibited the TGF-β/Smad3 signaling pathway, decreased α-SMA and SREBP1c expression, and increased AMPK (P<0.05).
Conclusions: Quercetin could significantly mitigate hepatic damage by modulating the expression of pro-inflammatory cytokines and fibrosis markers.
Objective: To examine the protective effects of green-synthesized zinc oxide nanoparticles with Berberis vulgaris L. fruit aqueous extract (BVZnONPs) on cyclophosphamide (CP)-induced nephrotoxicity in Wistar rats.
Methods: 35 Adult male Wistar rats were divided into 5 groups: normal, BVZnONPs (20 mg/kg), CP (100 mg/kg), and 2 cotreatment groups receiving CP with BVZnONPs (10 and 20 mg/ kg). All treatments were administered intraperitoneally for 28 days. Serum levels of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase, nitric oxide) and kidney function parameters (creatinine, total protein, blood urea nitrogen) were measured. The expressions of p53 and Bcl-2 proteins were assessed via immunohistochemical assay while kidney volume and substructures were estimated stereologically.
Results: CP induced nephrotoxicity with significant increases (P<0.05) in nitric oxide, creatinine, and blood urea nitrogen levels, and decreases (P<0.05) in catalase, superoxide dismutase, and glutathione peroxidase levels. It also increased p53 protein expression and decreased Bcl-2 protein expression. Treatment with BVZnONPs significantly increased (P<0.05) antioxidant enzyme levels and decreased nitric oxide levels in the 20 mg/kg group compared to CP. Blood urea nitrogen and creatinine levels were significantly reduced in the BVZnONPs-treated groups, with greater effects at 20 mg/kg. However, total protein serum levels were not significant (P>0.05) in the BVZnONPs-treated groups compared to CP.
Conclusions: These findings suggest that BVZnONPs can mitigate CP- induced nephrotoxicity, likely due to their antioxidant and anti-apoptotic properties, though longer treatment duration may be necessary for tissue- level improvements.
Objective: To explore the wound healing potential and chemical components of Lindernia ruellioides from Mizoram, India.
Methods: Plant extraction was conducted by cold maceration using chloroform, ethanol, and distilled water as solvents. To guarantee the safety of the plant extract, an acute dermal toxicity test was conducted before the experiment. Antioxidant assays were performed. Excision and incision wound models were used to assess the wound healing activities, including wound closure rate, epithelialization period, and tensile strength. A histopathological examination was carried out.
Results: Lindernia ruellioides contained bioactive compounds, such as mycolactone F, 1-O-octadec-9-enyl glycerol, reserpine, tetracosanoic acid, 2-O-caffeoylglucarate and several others which are found to possess various pharmacological activities. Acute dermal toxicity evaluation showed that the doses were deemed safe. Ethanol extract of Lindernia ruellioides (LREE) treatment significantly elevated glutathione, glutathione-S-transferase, and superoxide dismutase, and decreased malondialdehyde in a dose- dependent manner. It showed increased wound contraction rate, shorter epithelialization time, and elevated wound breaking strength in the LREE-treated group when compared with the control. In addition, the histological examination showed enhanced neovascularization, fibroblasts, and collagen in LREE-treated animals.
Conclusions: Lindenia ruellioides exhibits remarkable effects on wound healing. The study validates the traditional use of this plant in Mizoram region as a wound-healing agent.