co-fermentation-marsdenia-tenacissima-with-ganoderma-lucidum-anti

Co-Fermentation of <em>Marsdenia tenacissima</em> with <em>Ganoderma lucidum</em> and Anti-Lung Cancer Effect of the Fermentation Products

Marsdenia tenacissima (Roxb.) Wight et Arn. (MT), as a traditional Chinese and Dai herbal medicine, has anti-inflammatory, antibacterial, and antitumor ...

Minzu University of China

Key Laboratory of Ethnomedicine (Minzu University of China)

Marsdenia tenacissima is a traditional Chinese medicine that has been used since the Ming dynasty. It is famous for its apoptotic effects on lung cancer. However, limited information is available about the underlying mechanisms.

Mechanism of Marsdenia tenacissima extract promoting apoptosis of lung cancer by regulating Ca/CaM/CaMK signaling.

 Caulis is a traditional Chinese medicine, named Tongguanteng (TGT), that is often used for the adjuvant treatment of cancer. In our previous study, we reported that an ethyl acetate extract of TGT had inhibitory effects against adenocarcinoma A549 cells growth. To identify the components of TGT with anti-tumor activity and to elucidate their underlying mechanisms of action, we developed a technique for isolating compounds, which was then followed by cytotoxicity screening, network pharmacology analysis, and cellular and molecular experiments. We isolated a total of 19 compounds from a TGT ethyl acetate extract. Two novel steroidal saponins were assessed using an ultra-performance liquid chromatography-photodiode array coupled with quadrupole time-of-flight mass (UPLC-ESI-Q/TOF-MS). Then, we screened these constituents for anti-cancer activity against non-small cell lung cancer (NSCLC)  and obtained six target compounds. Furthermore, a compound-target-pathway network of these six bioactive ingredients was constructed to elucidate the potential pathways that controlled anticancer effects. Approximately 205 putative targets that were associated with TGT, as well as 270 putative targets that were related to NSCLC, were obtained from online databases and target prediction software. Protein-protein interaction networks for drugs as well as disease putative targets were generated, and 18 candidate targets were detected based on topological features. In addition, pathway enrichment analysis was performed to identify related pathways, including PI3K/AKT, VEGF, and EGFR tyrosine kinase inhibitor resistance, which are all related to metabolic processes and intrinsic apoptotic pathways involving reactive oxygen species (ROS). Then, various cellular experiments were conducted to validate drug-target mechanisms that had been predicted using network pharmacology analysis. The experimental results showed the four C21 steroidal saponins could upregulate Bax and downregulate Bcl-2 expression, thereby changing the mitochondrial membrane potential, producing ROS, and releasing cytochrome C, which finally activated caspase-3, caspase-9, and caspase-8, all of which induced apoptosis in A549 cells. In addition, these components also downregulated the expression of MMP-2 and MMP-9 proteins, further weakening their degradation of extracellular matrix components and type IV collagen, and inhibiting the migration and invasion of A549 cells. Our study elucidated the chemical composition and underlying anti-tumor mechanism of TGT which may be utilized in the treatment of lung cancer.

A Combined Phytochemistry and Network Pharmacology Approach to Reveal Potential Anti-NSCLC Effective Substances and Mechanisms in  (Roxb.) Moon (Stem).

Lung cancer is one of the malignant tumors with the fastest incidence rate and mortality growth and the greatest threat to human health and life.  is an antitumor of Chinese medicine. However,  has low bioavailability in the human body and most of its main active substances are aglycones, such as Tenacigenin A, Tenacigenin B. This study aims to produce biotransformation products rich in pungent saponins by using  as a fermentation medium of . Non-targeted metabolomics analysis was carried out on the fermentation products after the optimization process. A total of 249 differential metabolites were detected, and the content of saponins increased from 0.1% to 0.41% and most of them were tenacigenin. Furthermore, the biotransformation of C steroidal glycosides in  was the central reaction in this fermentation process. Pharmacodynamics resewed that the anticancer effect of  was significantly enhanced after fermentation, mainly through inhibiting the growth and apoptosis of cancer cells.

Article	Year
Mechanism of Marsdenia tenacissima extract promoting apoptosis of lung cancer by regulating Ca/CaM/CaMK signaling. Journal of ethnopharmacology\| PubMed ID: 31926315	2020
A Combined Phytochemistry and Network Pharmacology Approach to Reveal Potential Anti-NSCLC Effective Substances and Mechanisms in (Roxb.) Moon (Stem). Frontiers in pharmacology\| PubMed ID: 33994999	2021
Nontargeted metabolomics study and pharmacodynamic evaluation of bidirectional fermentation for with . Frontiers in pharmacology\| PubMed ID: 36386222	2022

Runtian Li

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