Deciphering the impact and mechanism of Trikatu, a spices-based formulation on alcoholic liver disease employing network pharmacology analysis and in vivo validation

Abstract

Trikatu Churna (TC) comprising Zingiber officinale rhizome, Piper longum, and Piper nigrum fruit, is effective in treating liver diseases and has high nutraceutical values. However, the efficacy of TC in treating alcoholic liver disease (ALD) and its mechanism remain largely unknown. This study evaluated the hepatoprotective effects of different doses of TC as well as to identify the bioactive components and determine their mechanism of action against ethanol-induced ALD. A compound-target network analysis model of TC was established to identify its potential bioactive compounds and pathways that might regulate its hepatoprotective effects. Further, in-vivo studies were performed to validate the potential of TC (200 mg/kg and 400 mg/kg b.w.) in the treatment and management of ALD. The study revealed that both the dosages of TC demonstrate significant (p > 0.0001) hepatoprotective effects by improving body weight, total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), serum alkaline phosphate (ALP), total cholesterol, total protein, globulin, albumin, and liver morphology. The High-performance thin-layer chromatography (HPTLC) fingerprinting of TC showed the presence of piperine. Network pharmacology identifies the role of TC in regulating various signaling processes including Advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in managing ALD. Based on the bioinformatics analysis, some of the key targets of TC were found to be Prostaglandin-Endoperoxide Synthase 2 (PTGS2) or Cyclooxygenase-2 (COX-2), Sirtuin 1 (SRT1), and caspase-3. These effects may serve as a novel therapeutic option for the treatment of ALD. These preclinical validation studies for the ethnopharmacological potential of TC in ALD treatment further paved the way for researchers to perform next-level translational and clinical studies. Further, in-depth experimental studies for the validation of these bioinformatics-based results will give a clearer picture of mechanisms.

The effect of chronic lithium treatment on hippocampal progenitor cells: Transcriptomic analysis and systems pharmacology

“…Network pharmacology attempts to establish a relationship between medicine and disease through targets. Applying the systems approach to investigate this relationship allows for discovering all possible drug targets and relevant beneficial or adverse effects simultaneously (Sharma, Jadhav, et al., 2022; Sharma, Singla, et al., 2022).…”

Green Alternatives in Treatment of Liver Diseases: the Challenges of Traditional Medicine and Green Nanomedicine

“…A large number of natural products with hepatoprotective activity have been reported; for example, for the treatment of ALD, individual plant extracts, [12][13][14] combinations of extracts, [15][16][17] and isolated compounds [18,19] have been tested, and have shown a favorable result (Figure 1). In particular, several molecules isolated from plants have also demonstrated their biological potential against different human conditions; however, certain studies have verified its natural origin does not exclude limitations or the possibility of inducing side effects in humans (Figure 1).…”

Qinggan Huoxue Recipe attenuates Alcoholic Liver Disease by suppressing PI3K/AKT signaling pathway based on network pharmacology

“…Kinsenoside reduced alcoholic liver injury by decreasing oxidative stress markers (3-Nitrotyrosine and 4-hydroxynonenal), inhibiting endoplasmic reticulum stress (ERS), and upregulated AMPK-dependent autophagy 9 . Network pharmacology helps to find that Trikatu Churna can pass through a variety of signal pathways, including advanced glycation end products (AGE-RAGE), Hypoxia-inducible factors (HIF-1), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-Kappa B), and Phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling to exert its anti-inflammatory, antioxidant and anti-apoptotic role in treating ALD 10 . Based on the investigation of the pathological factors of ALD patients, scholars summarized the TCM syndrome of different patients with ALD from the perspective of TCM, and put forward that “dampness-heat and blood stasis” is the basic pathogenesis mechanism of ALD, so as to establish “clearing liver and promoting blood circulation” as the basic treatment plan of ALD.…”