What Is the Benefit of Gotu Kola in Tami?

Centella asiatica in Tami is the dried whole herb of Centella asiatica L. Urban (family Apiaceae). First recorded in Shennong's Classic of Materia Medica, it is bitter, pungent and cold in nature, entering the liver, spleen and kidney channels. It has the effects of clearing away heat and dampness, detoxifying and reducing swelling. It has been used in clinical practice in China for more than 2,000 years, mainly for treating damp-heat jaundice, heatstroke diarrhea, hematuria and hematuria, boils and sores, bruises and injuries. Modern studies have shown that Centella asiatica has various effects, such as inhibiting scar hyperplasia, repairing skin damage, anti-depression, neuroprotection, anti-tumor, anti-ulcer and antibacterial, anti-inflammatory, etc. [1]. With the deepening of research on the chemical composition and pharmacological effects of Centella asiatica, the role of Centella asiatica in digestive system diseases has attracted the attention of more and more scholars at home and abroad.

This paper will review the chemical composition of Centella asiatica and the research progress in the treatment of digestive system diseases, providing a reference for subsequent research.

1 Research on the main chemical components of Centella asiatica

1.1 Triterpenoids

Triterpenoids are the earliest researched and most widely used components of Centella asiatica. The main components are triterpenoid saponins and triterpenoid acids. Triterpenoid saponins are mainly pentacyclic triterpenoid saponins. So far, 41 pentacyclic triterpenoid compounds have been isolated from Centella asiatica. with relatively high content in the following order: asiaticoside, madecassoside, Asiaticoside B, and a small amount of madecassoside, madecassoside, centelloside, and isocentelloside [2-4]. Weng Xiaoxiang et al. [5] were the first to isolate 15 dammarane-type tetracyclic triterpene saponins from Centella asiatica, including four new compounds: centelloside A, centelloside B, ginsenoside Mc and ginsenoside Y. The triterpenoid acids are less abundant, with madecassic acid and asiatic acid being the main components.

1.2 Volatile oil components

Zhang Wei et al. [6] identified 16 volatile components from Centella asiatica, accounting for 79.22% of the total peak area. The main volatile components are (E)-β-elemene (36.97%), caryophyllene (13.61%), geranylacetone (10.95%), α-cyperene (2.76%) and elemene (2.33%). Qin Lu Ping et al. [7] used steam distillation to extract the volatile oil of Centella asiatica whole plant, and analyzed it using gas chromatography-mass spectrometry (GC-MS). The results showed that 45 components were separated and identified, and the main components were caryophyllene (19.36%), farnesol (17.66%), elemene (4.42%), and longifolene (4.21%), etc.

1.3 Polyacetylene components

More than 20 polyacetylene compounds have been isolated from Centella asiatica. In 1973, Schulte first isolated 14 long-chain polyacetylene compounds from Centella asiatica and structurally identified 5 of them: C15 H20 O2, C17 H21 O3, C19 H27 O4, C16 H21 O2, C19 H28 O3; in 1975, Bohlman isolated two new polyacetylene compounds, C19 H28 O3 and C17 H24 O3, from Centella asiatica [3, 8]. Subsequently, Siddiqui et al. [9-10] isolated polyacetylene compounds such as centellin, asiaticin, centellicin, and cadiyenol from Centella asiatica.

In addition, centella asiatica also contains flavonoids, sterols, alkaloids, lignans, amino acids, fatty acids, sugars, tannins and polyphenols, including kaempferol, kaempferol-3-glucoside, kaempferic acid, quercetin, quercetin-3-glucoside, β-sitosterol, octacosyl octanoate, apigenin, chlorogenic acid, vanillic acid, succinic acid, glucose, etc. [11-13].

2 Research on the effect of Centella asiatica on digestive system diseases

2.1 Hepatoprotective effect

Asiaticoside can significantly reduce the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum of rats with liver fibrosis, as well as the level of hydroxyproline (Hyp) in liver tissue, significantly reduce liver tissue lesions, and significantly reduce collagen fibers. The effect is comparable to that of γ-interferon [14]. Asiaticoside has a significant protective effect on mice with acute liver injury caused by cecal ligation and puncture (CLP)-induced sepsis, and this effect may be related to the reduction of TNF-α release and cyclooxygenase-2 (COX-2) expression [15].

Asiatic acid protects the liver in three main ways: first, it suppresses the eukaryotic transcription factor nuclear factor-κB (NF-κB) signaling pathway to resist inflammatory reactions; second, it has a dual pharmacological effect of anti-inflammatory and anti-oxidative damage by activating ERK to upregulate the Nrf2/ARE signaling pathway; Third, it reduces oxidative stress, inflammation and hepatocyte apoptosis by regulating the Bcl-2/Bax signaling pathway [16-17]. In vivo experiments have shown that asiatic acid significantly improves liver fibrosis in mice with bile duct ligation (BDL), inhibits oxidative stress and inflammatory response, regulates bile acid metabolism, and improves liver tissue morphology and function. At the cellular level, asiatic acid can counteract GCDC-induced HL-7702 cell damage, inhibit the increase in ROS, reduce apoptosis, and promote the expression of Nrf2 [18]. In addition, asiatic acid can also inhibit the synthesis and secretion of collagen in HSC-T6 cells by upregulating the mRNA expression of Smad7 and PPARγ, thereby improving the pathological manifestations of liver fibrosis [19]; it can inhibit the activation of hepatic stellate cells and the synthesis of extracellular matrix by regulating the PI3K/AKT/mTOR signaling pathway [15].

Recent studies [20] have shown that madecassoside can reduce LPS/D-GalN-induced liver damage, protect liver function, inhibit the production of endogenous cytokines such as TNF-α, IL-1β, and IL-6, and restore the activity of antioxidant enzymes. Hydroxycentella asiatica saponin also significantly suppresses the protein levels of LPS-stimulated inducible nitric oxide synthase (iNOS) and COX-2 by blocking the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and NF-κB. In addition, madecassoside enhances the protein levels of heme oxygenase (HO)-1 and antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase) by upregulating Nrf2 in LPS-induced liver injury.

2.2 Protective effect on the pancreas

The asiaticoside extract can improve blood glucose in ZDF rats (Zucker Diabetic Fatty Rat), increase insulin levels, improve the inflammatory state of pancreatic tissue, and inhibit the apoptosis of pancreatic cells. The mechanism of action may be related to the inhibition of the abundance of Clostridium perfringens, Pseudoalteromonas, and Bacillus cereus in the ZDF rat, inhibit the expression of NADPH oxidase Phoxp22 subunit, iNOS, and Caspase-3 protein and gene in pancreatic tissue, and promote the expression of Bcl-2 protein and gene, etc. [21].

2.3 Anti-gastric ulcer effect

Both the water extract and alcohol extract of Centella asiatica have anti-gastric ulcer effects. Centella asiatica extract can mildly reduce gastric acidity, improve mesenteric microcirculation disorders in rats with gastric ulcers, and inhibit gastric juice secretion, gastric concentrated free acid and total acid, pepsin, and gastrointestinal smooth muscle contraction [22-23]. The mechanism may be related to its ability to reduce vascular permeability and the expression of myeloperoxidase (MPO), malondialdehyde (MDA), COX-2, inducible iNOS and IL-8 [24]; directly protect gastric mucosal cells, promote angiogenesis, and promote epithelial cell proliferation [25-26].

Centella asiatica total glycosides can stimulate the growth of granulation tissue in the gastric mucosa, promote the repair of inflammation and ulcer healing, and have a preventive and therapeutic effect on gastric ulcers to a certain extent, by increasing the content of IL-2 immunoglobulin IgA, IgG, and IgM, improving cellular and humoral immunity levels, and regulating the body's immune balance [27].

2.4 Treating inflammatory bowel disease

Centella asiatica extract has a significant ameliorating effect on acetic acid-induced inflammatory bowel disease in rats. The isolated component 3,5-dicaffeoyl-4-O-coumaroylquinic acid in Centella asiatica can reduce the levels of NF-κB, iNOS, nitrotyrosine, PARP, proMMP-9 and proMMP-2 in the colon tissue of rats with colitis, and reduce the upregulation of ICAM-1 and the expression of P-selectin [28-29].

Hydroxycentella asiatica saponins, hydroxycentella asiatica acid, asiaticoside, and asiatic acid can all relieve DSS-induced colitis, with hydroxycentella asiatica saponins and hydroxycentella asiatica acid being more effective than asiaticoside and asiatic acid [30]. Madecassoside can inhibit the activation of NLRP3 inflammasomes in mice with colitis and reduce the release of inflammatory factors such as TNF-α, IL-1β, and IFN-γ [31]; while madecassic acid can reduce the percentage of Th17 cells in mice with colitis, down-regulate the expression of ACC1, RORγt, IL-17A, IL-17F, IL-21, IL-22 expression, promote the migration of Th17 cells to Treg cells, increase Treg cell percentage, increase Foxp3, IL-10 expression, but have no significant effect on Th1 and Th2 cells [30].

2.5 Anti-cancer effect

Centella asiatica has no toxic effect on normal cells and is cytotoxic to tumor cells. It can be used to treat liver cancer, gastric cancer and colon cancer. Centella asiatica juice can lead to a decrease in the expression of the c-myc gene and an increase in the expression of the c-fos and c-erbB-2 genes in tumor cells, thereby reducing the proliferation of liver cancer cells and increasing liver cancer cell apoptosis [32]. Centella asiatica extract can inhibit the proliferation of human gastric cancer SGC-7901 cell line, inhibit its adhesion and invasion in vitro, and induce apoptosis [33]. Centella asiatica water extract can inhibit colon cancer by regulating the proliferation of colon crypt cells and inducing apoptosis [34]. Centella asiatica acid has an inhibitory effect on colon cancer induced by 1,2-dimethylhydrazine (DMH), which is mainly attributed to the detoxification effect of centella asiatica acid on carcinogens, maintenance of antioxidant balance, regulation of LPO markers, and phase I and II detoxification enzymes [35].

In summary, Centella asiatica is complex and diverse in composition, with the highest content of asiaticoside, madecassoside and asiatic acid. The type and content of the components contained in Centella asiatica vary, which may be related to the extraction method, place of origin and time of harvest of the medicinal herb [36]. Centella asiatica has anti-inflammatory and wound-healing effects, and can be used to protect the liver and pancreas, treat gastric ulcers and inflammatory bowel disease, and fight cancer. However, most of the research on Centella asiatica in relation to digestive diseases has been limited to pharmacological experiments, with few clinical studies reported. Therefore, in the future, while improving experimental skills and updating experimental methods to study its mechanism of action, further in-depth clinical research should be conducted to better demonstrate the clinical application value of Centella asiatica in digestive diseases.

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