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The interaction between herbal remedies and drugs is a fascinating phenomenon that might cause therapeutic complications in patients. Warfarin is an anticoagulant drug that provides anti-blood-clotting effects by inhibiting the formation of vitamin K-dependent coagulation factors, and warfarin interacts with the nuclear receptor PXR, subsequently modulating cytochrome P450 during the metabolism process. St. John's wort, an herbal medicine with antidepressant effects, can alter the pharmacokinetics of warfarin. Thymoquinone is one of the active compounds in N. sativa and has pharmacological activities such as anticoagulant, antidiabetic, diuretic, antidepressant, and anti-inflammatory effects. In this study, we investigated the compounds in Nigella sativa ( N. sativa) against pregnane X receptor (PXR) and evaluated the impact of thymoquinone (TQ) administration on PXR expression in HepG2 cells. The molecular docking analysis was conducted utilizing the Molecular Operating Environment (MOE) with the PXR (PDB ID: 7AXJ). At the same time, the PXR gene expression was measured using RT-PCR instruments. The RMSD value in docking represents the deviation criteria between the native ligand position and the redocking position result, indicating the capability of MOE and PDB qualification for performing molecular docking. The docking analysis showed that warfarin had the strongest binding energy (7AXJ -6.0507) by forming hydrogen binding type on Arg410. Despite TQ being the major component, it also displayed a high affinity for the two PDB IDs (7AXJ -4.5962). Furthermore, the concurrent administration of warfarin and TQ (19.27 μM) in HepG2 cells showed a significant reduction in the relative mRNA expression of the PXR gene. Given the above-mentioned findings, our study adequately enables us to predict the mechanism behind herb-drug interactions (HDIs) implicating N. sativa, specifically the TQ compound to warfarin metabolism via the activation of the PXR receptor. [ABSTRACT FROM AUTHOR]

Preclinical test is a stage in evaluating potential drug candidates for diabetes mellitus (DM). However, developing an animal model that accurately replicates the various pathophysiological and etiological aspects of DM as seen in humans presents significant challenges. To induce diabetes, streptozotocin (STZ) in single doses or combination with nicotinamide (NIC) is often used. Treating diabetes conditions has a low success rate, compounded by the complexity of numerous affected biochemical profiles, presenting a significant research challenge. Therefore, this research aimed to determine the biochemical and triglyceride-glucose index (TyG) profile in high doses of STZ-NIC-induced diabetes in the rat model. The population consisted of 18 rates divided into three groups, each containing six. Group I (the normal group) consisted of healthy rats who were given standard feed and drink. In groups II and III, diabetes was induced intraperitoneally with 50 and 65 mg/kg of STZ in addition to 230 mg/kg of NIC. Observations were made for 6 weeks after the rats were diagnosed with diabetes having blood glucose levels of ≥ 250 mg/dL 72 hours after STZ-NIC induction. The data were evaluated statistically by one-way analysis of variance (ANOVA), followed by the least significant difference (LSD) test (p ≤ 0.05). The result showed significant differences in blood biochemistry, specifically in the parameters of blood glucose, SGPT, and SGOT with increasing doses of STZ-NIC (p<0.05), but not in total cholesterol, triglycerides, albumin, total protein, and TyG ( p<0.05). The high doses of STZ-NIC administration can produce DM models with different blood biochemical profiles but not in TyG. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) has been linked to a number of long-term problems caused by diabetes mellitus. Inflammatory and oxidative stress pathways contribute to DN development and progression. Many studies have shown the preventive advantages of diets rich in substances like antiinflammatory and antioxidant elements like omega-3 fatty acids (n-3 FA) in preventing DN. Milkfish (Chanos chanos F.), patin (Pangasius micronema Blkr.), and snakehead fish (Chana striata Bloch) are fish oils which are known to contain n-3 FA. This study aims to evaluate the nephroprotective effect of three types of fish oils in a rat model of diabetes mellitus. Thirty male rats were used in this study. The animals were randomly divided into six groups (n = 5): the non-diabetic group, the diabetes mellitus group, the diabetic with 150 mg/kg metformin orally group, the diabetic with 1000 mg/kg milkfish oil orally group, the diabetic with 1000 mg/kg patin fish oil orally group, and the diabetic with 1000 mg/kg snakehead fish oil orally group. Diabetes models were induced using 65 mg/kg streptozotocin and 230 mg/kg nicotinamide intraperitoneally. The test was carried out for 8 weeks, followed by the observation of the biochemical profiles of blood, urine, oxidative stress, and the immunohistochemistry of the kidneys. A normally and homogeneously distributed test followed by a one-way analysis of variance (ANOVA) and the LSD post hoc test were used to analyse data at P 0.05. The results showed that serum creatinine levels did not differ significantly after the administration of milkfish, catfish, and snakehead fish oil for 8 weeks (p≥0.05). Different results were shown where the levels of serum BUN, uric acid, urine urea, and microalbumin urine were significantly different after administration of the three types of fish oil (p≤0.05). The same results were shown in oxidative stress (superoxide dismutase, glutathione, and malondialdehyde) and inflammation (interleukin-6 and tumor necrosis factor-α) profiles (p≤0.05). [ABSTRACT FROM AUTHOR]

Bengkoang (Pachyrhizus erosus (L.) Urban) contains phytosterol and the isoflavone daidzein, which are thought to have immunomodulatory activity. There have been no studies reporting on the immunomodulatory effects of bengkoang extract containing polar and semi-polar compounds, such as phytosterols and isoflavone-like compounds. The objective of this study was to evaluate the immunomodulatory effects of bengkoang extracts, including petroleum ether extract (PEE), methanol extract (ME), and the ethyl acetate fraction (EAF) of bengkoang, in vitro. The immunomodulatory effects of PEE, ME, and EAF of bengkoang were determined according to the phagocytic activity of macrophages based on phagocytosis of latex beads, lymphocyte proliferation, and detection of cytokine production of tumor necrosis factor-α (TNF-α) interleukin-6 (IL-6), and interleukin-10 (IL-10) levels. Results: The phagocytic index and phagocytic capacity of ME, PEE, and EAF of bengkoang on macrophage cells were significantly increased (p < 0.05), whereas on lymphocyte proliferation, ME showed a trend of increasing activity (p < 0.05). On the other hand, the PEE effect showed a decreasing trend of activity, and the others had no significant effect on lymphocyte proliferation (p > 0.05), and ME of bengkoang enhanced the levels of the cytokines TNF-α and IL-6. In contrast, PEE and EAF of bengkoang decreased TNF-α and IL-6 levels compared with the control group. All of the bengkoang extracts decrease the production of the anti-inflammatory cytokine IL-10. In conclusion, this study showed that PEE, ME, and EAF of bengkoang could increase the non-specific immune response (phagocytic activity) but had a lesser effect on the specific immune response (lymphocyte proliferation). The ME of bengkoang acts as an immunostimulant by increasing the levels of the inflammatory cytokines TNF-α and IL-6 and decreasing those of the antiinflammatory cytokine IL-10. Further investigation of in vivo immunomodulatory effects is needed to determine its effect on systemically innate and adaptive immune responses. [ABSTRACT FROM AUTHOR]