JP-7856315-B2 - Use of terpenoids in the treatment or prevention of fibrous diseases

Inventors

• ウー，イェー－ビー
• ロ，ジャー－メン
• リアン，ホイ－ジュ
• リン，ペイ－シン

Assignees

• アージル・バイオテック・ホールディング・カンパニー・リミテッド

Dates

Publication Date

20260511

Application Date

20210519

Priority Date

20200519

Claims (4)

1. A composition comprising an anisomeles indica extract for the prevention or treatment of fibrotic conditions, wherein the fibrotic condition is selected from renal fibrosis, vascular fibrosis, and pulmonary fibrosis.
2. Anisomeles indica extract is given by the following formula: The composition according to claim 1, comprising at least one compound selected from the group consisting of compounds represented by and combinations thereof.
3. The following formulas are used to prevent or treat fibrous conditions: A composition comprising an effective amount of a compound selected from the group consisting of the compounds shown and combinations thereof, A composition in which the fibrotic condition is selected from renal fibrosis, vascular fibrosis, and pulmonary fibrosis.
4. The composition according to claim 1 or 3, wherein the composition further reduces renal dysfunction and renal damage .

Description

This invention relates to herbal terpenoids derived from extracts of Antrodia camphorata and Anisomeles indica, particularly to medicinal and edible formulations for effectively alleviating fibrotic diseases. Fibrous proliferative disorders are a growing problem for individuals and are a common pathological consequence of many persistent inflammatory diseases, including pulmonary fibrosis, progressive kidney disease, cirrhosis, atherosclerosis, and benign prostatic hyperplasia. Impaired renal repair after acute kidney injury can induce fibrosis, ultimately leading to the development of chronic kidney disease. Kidney injury activates pluripotent progenitor cells to repair tissue. However, these pluripotent progenitor cells become dysfunctional, inducing fibrinolytic repair, as the injury supports the development of renal fibrosis. The development of renal fibrosis is a progressive process that ultimately leads to end-stage renal failure, a catastrophic impairment requiring dialysis or kidney transplantation. Non-alcoholic fatty liver disease (NAFLD) is a major form of chronic liver disease with a significant unmet need. Non-alcoholic steatohepatitis (NASH), a progressive variant of NAFLD, can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD and NASH are attracting attention throughout the medical community, particularly due to the increasing prevalence of diabetes and obesity in the global population. When clinically evaluating patients with abnormal aminotransferase levels, NAFLD and its spectrum should always be considered, especially if the patient is obese or diabetic. While the prognosis for simple NAFLD is generally benign, there is a risk of progression to cirrhosis if fibrosis, hepatocyte hypertrophy, inflammation, and Mallory bodies are present. Autoimmune hepatitis (AIH) is a chronic liver disease characterized by inflammation of liver cells, although it does not have a clear etiology. Severe AIH can progress to cirrhosis, hepatocellular carcinoma, or death. Cirrhosis occurs in approximately 40% of patients treated for autoimmune hepatitis, depending on the observation period. Antifibrotic therapy can complement the anti-inflammatory and immunosuppressive effects of current regimens, and these regimens are emerging as treatments that are expected to shift the focus of autoimmune hepatitis treatment towards the prevention, stabilization, and recovery of liver fibrosis. Atherosclerosis, one of the major causes of cardiovascular disease progression, involves vascular fibrosis. Vascular fibrosis involves the accumulation of extracellular matrix (ECM) proteins, particularly collagen and fibronectin in the vascular media, contributing to structural remodeling and scar formation. A deficiency of elastin or an excess of collagen in the vascular wall leads to vascular fibrosis and increased stiffness. In benign prostatic hyperplasia (BPH), the deposition of collagen fibers in the prostate gland serves to replace damaged muscle fibers, but it results in stiffness and weakness of the muscle tissue, as well as deposition of prostatic fluid in the glandular ducts. Prostatic fibrosis plays a central role in the development of bladder outlet obstruction in aging men. Antrodia camphorata (AC), a medicinal fungus, is a well-known Chinese folk medicine with numerous biological activities, particularly antitumor effects in in vitro cancer cells and in vivo animal models. Its diverse bioactive compounds have led to its consideration as an efficient alternative plant-based therapeutic agent or adjuvant for cancer treatment and immune-related diseases. To date, a total of 225 compounds, including macromolecules (nucleic acids, proteins, and polysaccharides), small molecules (benzenoides, lignans, benzoquinones, and malein/succinic acid derivatives), terpenoids (lanostan triterpenes, ergostan triterpenes, diterpenes, monoterpenes, and steroids), nucleotides (nucleic acid bases and nucleosides), fatty acids, and fatty acid esters, have been isolated, identified, and structurally elucidated. Cumulative in vitro and in vivo studies have revealed its anti-diabetic and anti-hyperlipidemia, anti-hypertensive, anti-inflammatory, antioxidant, antibacterial, cardiovascular disease prevention, immunomodulatory, hepatoprotective, and neuroprotective effects. However, the efficacy of Antrodia camphorata and its components in the treatment of fibrosis has not been evaluated. Anisomeles indica, commonly known as "Indian Catmint," is a source of medicinal compounds and possesses a variety of pharmacological effects. This plant has traditionally been used as an analgesic, anti-inflammatory, and for treating skin problems. Medicinally, it has been proven to have various pharmacological activities, including antioxidant, antibacterial, anti-HIV, anti-Helicobacter pylori, and anti-cancer activity. It is also used for chronic rheumatism. Further research has revealed the presence of various phytochemicals, primarily triterpe