Studies Examine Chinese Medicine's Impact on Diseases

Traditional Chinese Medicine (TCM) compounds have demonstrated significant clinical efficacy against various diseases. However, their widespread use is still limited, mainly due to the complexity in their formulation and lack of sufficient pharmacological and safety-related data.

To address this gap, a new issue of the Journal of Pharmaceutical Analysis presents three independent studies which assessed the potency of TCM-based compounds for various human diseases, along with their molecular mechanisms of action.

The accumulation of excess fat in the liver leads to non-alcoholic fatty liver disease (NAFLD). Oridonin (ORI), a TCM derived from the Chinese herb Rabdosia rubescens, exhibits various pharmacological activities, including anti-inflammatory effects. An article available online on 21 August 2023 and published in Volume 13, Issue 11 of the journal in November 2023, explores the molecular mechanisms underlying the anti-inflammatory effects of ORI. The study reveals that ORI regulates lipid homeostasis in the liver by maintaining the balance between triglyceride (TG) and phosphatidylethanolamine (PE), through modulation of adipose triglyceride lipase (ATGL) and ethanolamine phosphotransferase 1 (EPT1) expression via the liver X receptor alpha (LXRα) signaling pathway. "When the TG-PE lipid balance is disturbed, the seesaw tilts towards TG, increasing the risk of NAFLD. Restoring lipid homeostasis using compounds like ORI can alleviate lipid accumulation and liver cytotoxicity ," explains Professor Lan Tang.

The efficacy of radiotherapy for treating lung cancer is compromised as a result of tumor heterogeneity. Radiosensitizers help prime tumor cells and improve their response to radiation. Now, in an article available online on 7 June 2023 and published in Volume 13, Issue 11 of the journal in November 2023, researchers explored the tumor suppressive and radiosensitizing effects of ginsenoside Rg5, a bioactive compound of ginseng. They found that ginsenoside Rg5 induced cell-cycle arrest and enhanced radiation-induced cell death by modulating heat shock protein interactions and autophagy pathways. Ginsenoside Rg5 interacts with heat shock protein alpha (HSP90α) with high affinity and reduces the binding between HSP90 and cell division cycle 37 (CDC37), promoting HSP90-CDC37 client protein degradation. "Ginsenoside Rg5 can be potentially developed into a new drug for improving the sensitivity of lung cancer and other types of tumors to radiation therapy," the authors explain.

Diabetic retinopathy (DR) is the leading cause of blindness and visual impairment in adults and is characterized by the activation of oxidative stress pathways in response to high glucose. In a study available online on 12 May 2023 and published in Volume 13, Issue 11 of the journal in November 2023, researchers synthesized a polymeric drug complex by combining a natural flavonoid antioxidant known as dihydromyricetin (DMY) with iron (Fe) ions in nano-coordinated polymer particles (NCPs). Their findings demonstrate that Fe-DMY NCPs alleviate glucose-induced oxidative damage and reverse the pathological features of DR by decreasing the expression of key proteins involved in microvascular dysfunction. Further mechanistic validation also suggested that Fe-DMY NCPs could inhibit the activation of Poldip2-Nox4-H2O2 signaling pathway and down-regulate important vascular function indicators, such as VCAM-1, HIF-1α, and VEGF. Explaining its applications, the authors say, "We report for the first time the synthesis and validation of ultra-small Fe-DMY NCPs particles formed by coupling DMY with low-toxicity iron ions. Fe-DMY complexes bear the potential to alleviate the impact of DR on vision, thus improving the quality of life of affected individuals"

In summary, these studies provide a scientific basis for the development of TCM-based compounds into effective targeted therapies for various diseases.

***

Reference

Titles of original papers:

1. Oridonin restores hepatic lipid homeostasis in an LXRa-ATGL/EPT1 axis-dependent manner
2. Ginsenoside Rg5 enhances the radiosensitivity of lung adenocarcinoma via reducing HSP90-CDC37 interaction and promoting client protein degradation
3. Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H₂O₂ pathway and alleviating diabetic retinopathy

DOI:

1. https://doi.org/10.1016/j.jpha.2023.08.010
2. https://doi.org/10.1016/j.jpha.2023.06.004
3. https://doi.org/10.1016/j.jpha.2023.05.002