The Pharmacological Effects and Clinical Applications of Epipremnum Aureum in the Treatment of Liver Diseases

Sedum sarmentosum, also known as trailing jade plant, hanging jade plant, or dogtooth half-branch, is the dried whole plant of Sedum sarmentosum, a member of the Crassulaceae family. It is harvested in summer and autumn, impurities are removed, and then it is dried. It has a sweet and mild taste, with a slightly cool nature, and is associated with the liver, gallbladder, and small intestine meridians. It has the effects of clearing heat and detoxifying, promoting diuresis and reducing swelling, eliminating abscesses and promoting tissue regeneration, as well as lowering alanine aminotransferase levels. It is mainly used for the treatment of damp-heat jaundice, urinary difficulties, abscesses, sores, and acute and chronic hepatitis.

Sedum sarmentosum mainly contains flavonoids, sterols, alkaloids, triterpenes, amino acids, and volatile oils. Pharmacological experiments have shown that it has hepatoprotective, anti-inflammatory, antioxidant, antitumor, immune-modulating, and muscle-strengthening effects. Sedum sarmentosum has unique advantages in the treatment of liver diseases and is widely used clinically for the treatment of viral hepatitis, fatty liver disease, drug-induced liver injury, and other conditions.

Pharmacological Effects of Sedum sarmentosum in Liver Disease Treatment

1. Hepatoprotective and Enzyme-Lowering Effects, Anti-Liver Injury

Sedum sarmentosum exerts hepatoprotective and anti-liver injury effects by downregulating the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD), and the expression of TGF-β1 mRNA and protein, while upregulating the expression of miR-124. The total flavonoids in Sedum sarmentosum are its important active ingredients for hepatoprotection and enzyme-lowering, significantly reducing ALT and AST levels in mice, demonstrating a clear protective effect on the liver. Research has found that hyperin and 5,4′-dihydroxy-8,3′-dimethoxyflavone-3,7-di-O-β-D-glucoside, flavonoid compounds in Sedum sarmentosum, have significant protective effects on liver cell damage within a certain concentration range. Total flavonoids from Sedum sarmentosum can protect against hepatocyte injury and promote liver function recovery by reducing ALT, AST, hyaluronic acid (HA), and laminin (LN) levels in rats, and also show good protective effects on experimental liver fibrosis in rats. Extracts of Sedum sarmentosum protect rats with α-naphthylisothiocyanate (ANIT)-induced liver injury models, with its protective mechanism related to promoting antioxidant defense of nuclear factor E2-related factor 2 (Nrf2) and inhibiting the inflammatory response of nuclear factor-κB (NF-κB). Some studies have found that the decoction of Sedum sarmentosum has a protective effect on rats with carbon tetrachloride-induced liver injury models, and its mechanism of action is related to anti-lipid peroxidation. Total flavonoids from Sedum sarmentosum can effectively reverse liver fibrosis induced by carbon tetrachloride in rats, with its mechanism of action related to upregulating the expression of tumor suppressor factor Smad7 mRNA and protein and downregulating the expression of transforming growth factor β (1 TGF-β1) mRNA and protein in liver tissue. Extracts of Sedum sarmentosum can protect against liver injury by reducing ALT, AST, MDA, and SOD levels in liver injury model mice.

2.Anti-Liver Fibrosis

Sedum sarmentosum exerts anti-liver fibrosis effects by inhibiting the activity of the TGF-β/TβR/Smad signaling pathway and the activation of hepatic stellate cells. In the process of chronic liver disease developing into liver cirrhosis, liver fibrosis is an inevitable step, and the differentiation of hepatic stellate cells into myofibroblasts is the key to fibrosis formation. Research has found that total flavonoids from Sedum sarmentosum can promote apoptosis of hepatic stellate cells by inhibiting B-cell lymphoma 2 (Bcl-2) and promoting the expression of Bcl-2-associated X protein (Bax) and caspase-3 protein, thereby exerting anti-liver fibrosis effects. Dihydroflavones in Sedum sarmentosum can improve carbon tetrachloride-induced liver fibrosis in rats by inhibiting the activity of the TGF-β/TGF-β receptor (TβR)/Smad signaling pathway and inhibiting epithelial-mesenchymal transition. Total flavonoids from Sedum sarmentosum can significantly improve the degree of liver fibrosis in rats, and its mechanism of action may be related to inhibiting the Smads pathway and the activation of hepatic stellate cells.

3.Anti-Cholestasis

Sedum sarmentosum exerts anti-cholestasis effects by participating in the transport and synthesis of bile acids, reducing ALT, AST, alkaline phosphatase (ALP) activity, and total bilirubin (TBIL) content. Cholestasis is caused by disorders in bile production, leading to the retention of toxic bile components (including bile salts) within cells. If not treated promptly, it can lead to liver fibrosis, cirrhosis, and ultimately liver failure. Research has found that most neonatal liver diseases are primarily related to intrahepatic cholestasis. Sedum sarmentosin can exert anti-cholestasis effects by participating in the transport and synthesis of bile acids in model rats. Additionally, sedum sarmentosin can also reduce ALT, AST, ALP activity, and TBIL content in cholestatic model rats, thereby exerting anti-cholestasis effects.

4.Inhibition of Hepatocellular Carcinoma Cell Proliferation

Sedum sarmentosum exerts an inhibitory effect on the proliferation of hepatocellular carcinoma cells by suppressing the expression of STAT-3, Mcl-1, and Bcl-2, and increasing the number of hepatocellular carcinoma cells in the G1 phase. Hepatocellular carcinoma is one of the most common malignant tumors in the world and also the most common fatal cancer. Research has found that the alcohol extract of Sedum sarmentosum can inhibit the proliferation of hepatocellular carcinoma cells by suppressing the signal transducer and activator of transcription 3 (STAT-3) signaling pathway and the expression of myeloid cell leukemia protein 1 (Mcl-1) and Bcl-2, ultimately inducing apoptosis of hepatocellular carcinoma cells. In vitro studies using human hepatocellular carcinoma cell lines have found that crude alkaloids extracted from Sedum sarmentosum can significantly inhibit the proliferation of hepatocellular carcinoma cells at certain concentrations, and its mechanism of action is related to increasing the number of hepatocellular carcinoma cells in the G1 phase. The aqueous extract of Sedum sarmentosum can induce apoptosis of hepatocellular carcinoma cells. The polysaccharide component of Sedum sarmentosum can inhibit the growth of human hepatocellular carcinoma Huh-7 cells, suggesting a possible anti-hepatocellular carcinoma effect.

Clinical Applications of Sedum Sarmentosum

As a traditional Chinese medicinal herb for nourishing the liver and reducing enzyme levels, Sedum sarmentosum is known as a "liver protector." In ancient China, Sedum sarmentosum has been used to treat chronic hepatitis. With a long history and practice of clinical application, Sedum sarmentosum possesses the effects of promoting diuresis and jaundice regression, as well as clearing heat and detoxifying. In clinical practice, it has been formulated into various dosage forms such as Sedum sarmentosum granules, Sedum sarmentosum sustained-release pellets, and compound Sedum sarmentosum capsules to treat various acute and chronic hepatitis, including viral hepatitis, fatty liver disease, drug-induced liver injury, terminal liver diseases, and their complications.

1. Treatment of Viral Hepatitis

Viral hepatitis can be classified into types A, B, C, D, and E. In modern clinical practice, drugs commonly used to treat viral hepatitis include Entecavir (ETV), Tenofovir Disoproxil Fumarate (TDF), Tenofovir Alafenamide (TAF), Elbasvir (EBR), Grazoprevir (GZR), Glecaprevir (GLE), and Pibrentasvir (PIB). However, due to the relatively high side effects of chemical drugs, they are often used in combination with traditional Chinese medicine. Clinical studies have found that the combination of Compound Sedum Sarmentosum Capsules and Tenofovir Disoproxil Fumarate in treating chronic hepatitis B viral hepatitis effectively reduced patients' liver function indicators ALT, AST, and total bilirubin (TBIL) levels compared to before treatment, indicating that the combination of these two drugs can effectively treat chronic hepatitis B viral hepatitis. The use of a compound formula containing Sedum Sarmentosum (composed of Sedum Sarmentosum, fried atractylodes, white poria cocos, turmeric, and other traditional Chinese medicinal herbs) to treat mild to moderate hepatitis B viral hepatitis found that the compound can restore patients' liver function to normal. Clinical studies have also shown that Huojian Gan Tang (a traditional Chinese medicine formula with Sedum Sarmentosum as the main ingredient) combined with Entecavir Dispersible Tablets can enhance patients' immune function and play a role in treating chronic hepatitis B viral hepatitis. A clinical study using the Lishi Huoxue formula (containing 30g of Sedum Sarmentosum) combined with interferon and ribavirin in treating chronic hepatitis C viral hepatitis found that the combination of these three drugs can significantly treat chronic hepatitis C viral hepatitis in elderly patients.

2.Treatment of Fatty Liver Disease

The compound formula containing Sedum Sarmentosum can be clinically used to treat fatty liver disease, and it also has significant therapeutic effects on non-alcoholic fatty liver disease. Clinical studies have found that the combination of Sedum Sarmentosum and Qianggan Capsules in treating non-alcoholic fatty liver disease effectively improves patients' blood lipid levels and liver function, which is of great significance for promoting the recovery of patients with non-alcoholic fatty liver disease. The use of Xiaozhi Yigan Decoction (containing 10g of Sedum Sarmentosum) in treating non-alcoholic fatty liver disease has shown that this compound formula can reduce the incidence of liver fibrosis and cirrhosis in patients. Clinical studies have also revealed that Hugan Quzhi Tang (containing 30g of Sedum Sarmentosum) can restore liver function in patients with non-alcoholic fatty liver disease. In addition, Sedum Sarmentosum also has a certain improvement effect on patients with non-alcoholic fatty liver disease accompanied by damp-heat accumulation syndrome.

3.Treatment of Drug-induced Liver Injury

Apart from its significant efficacy in treating fatty liver disease, Sedum Sarmentosum also provides certain protection and relief for drug-induced liver injury. Drugs such as isoniazid, rifampicin, and pyrazinamide are effective in treating tuberculosis, but they all have certain hepatotoxic effects. Studies have found that for some tuberculosis patients, administering Sedum Sarmentosum as adjunctive treatment when initiating antituberculosis drugs in the early stages of the disease significantly reduces the incidence of liver injury caused by these drugs. Patients with liver injury induced by antituberculosis drugs who take Shuganjiedu Fang (a decoction-free granule formula containing 20g of Sedum Sarmentosum) experience significant improvement in their symptoms.

4.Treatment of Terminal Liver Diseases and Their Complications

Both viral and non-viral liver diseases, if not treated promptly, will eventually lead to late-stage liver diseases such as liver failure, cirrhosis, and liver cancer, as well as various complications like ascites and gastrointestinal bleeding. Clinical studies have found that the use of Compound Shecao Pills (containing 15g of Sedum Sarmentosum) in treating cirrhosis significantly improved patients' liver fibrosis markers (including hyaluronic acid (HA), type III procollagen N-terminal peptide (PⅢNP), type IV collagen (CIV), and laminin (LN)) and liver function. Another study using a traditional Chinese medicine compound (containing 15g of Sedum Sarmentosum) to treat ascites due to cirrhosis revealed that after taking the medication, patients' ascites reduced by nearly half, and their overall condition also improved significantly.

As a traditional Chinese medicine, Sedum Sarmentosum boasts advantages such as low toxicity and side effects, as well as low cost. In the treatment of liver diseases, it exhibits pharmacological effects including protecting the liver, reducing enzymes, resisting liver injury, fighting liver fibrosis, alleviating intrahepatic cholestasis, and inhibiting the proliferation of liver cancer cells. Clinically, it is often used in the form of traditional Chinese medicine compounds to treat viral hepatitis, fatty liver disease, drug-induced liver injury, terminal liver diseases, and their complications. However, most of the current research on the use of Sedum Sarmentosum in treating liver diseases remains at the level of animal or cell experiments, lacking high-quality clinical evidence and suffering from a small number of case samples. Therefore, conducting large-sample, randomized controlled clinical studies on the use of Sedum Sarmentosum in treating liver diseases is of significant importance for future research.

References

[1] Yang Yingying, Wan Xinhuan, Liu Yingnan, Guo Lingyan, Zhou Changzheng. Research Progress on Chemical Constituents and Pharmacological Effects of Sedum Sarmentosum [J]. China Journal of Chinese Materia Medica, 2020, 45(18): 4341-4348. DOI: 10.19540/j.cnki.cjcmm.20200623.601.

[2] Yin Yiming, Wan Xinhuan, Zhao Fangshu, Ni Wenting, Li Baohong, Wang Xiaoqing, Sun Yunhong, Tian Jingzhen. Research Progress on Pharmacological Effects and Clinical Applications of Sedum Sarmentosum in the Treatment of Liver Diseases [J]. China Pharmacy, 2021, 32(19): 2429-2432.

About the Author: Xiaomichong, a researcher in pharmaceutical quality, has been dedicated to pharmaceutical quality research and verification of drug analysis methods for a long time. Currently, she works in a large domestic pharmaceutical research and development company, engaged in drug inspection analysis and verification of analytical methods.