Comprehensive landscape-style investigation of the molecular mechanism of acupuncture at ST36 single acupoint on different systemic diseases.

The principle of acupoint stimulation efficacy is based on traditional meridian theory. However, the molecular mechanisms underlying the therapeutic effects of acupoints in treating diseases remain unclear in modern scientific understanding. In this study, we selected the ST36 acupoint for investigation and summarized all relevant literature from the PubMed database over the past 10 years. The results indicate that stimulation of ST36 single acupoints has therapeutic effects mainly in models of respiratory, neurological, digestive, endocrine and immune system diseases. And it can affect the inflammatory state, oxidative stress, respiratory mucus secretion, intestinal flora, immune cell function, neurotransmitter transmission, hormone secretion, the network of Interstitial Cells of Cajal (ICC) and glucose metabolism of the organism in these pathological states. Among them, acupuncture at the ST36 single point has the most prominent function in regulating the inflammatory state, which can mainly affect the activation of MAPK signaling pathway and drive the "molecular-cellular" mode involving macrophages, T-lymphocytes, mast cells (MCs) and neuroglial cells as the core to trigger the molecular level changes of the acupuncture point locally or in the target organ tissues, thereby establishing a multi-system, multi-target, multi-level molecular regulating mechanism. This article provides a comprehensive summary and discussion of the molecular mechanisms and effects of acupuncture at the ST36 acupoint, laying the groundwork for future in-depth research on acupuncture point theory.

Research progress on the molecular mechanism of electroacupuncture at "Zusanli" (ST36) for regulating gastrointestinal dysfunction. / 电针"足三里"è°ƒèŠ‚èƒƒè‚ åŠŸèƒ½å¼‚å¸¸çš„åˆ†å­æœºåˆ¶ç ”ç©¶è¿›å±•.

Gastrointestinal dysfunction is manifested as digestive symptoms. Clinically, Zusanli (ST36) is crucial in the acupoint prescriptions of acupuncture no matter which type of the disease is differentiated in traditional Chinese medicine, but the underlying mechanism remains to be explored. Aiming to summarize the current status of the researches in terms of ameliorating gastrointestinal mucosal damage and regulating gastrointestinal motility disorders, we systematically reviewed the basic researches on the intervention with electroacupuncture (EA) at "ST36" in treatment of the diseases related to gastrointestinal dysfunction in the past 5 years, after searching the articles from Chinese and English databases. The results suggest that EA at ST36 may regulate the local gastrointestinal inflammation, oxidative stress and immune microenvironment to relieve gastrointestinal mucosal damage and adjust gastrointestinal motility disorders by means of modulating the central and peripheral nerve signaling as well as the function of mast cells and Cajal interstitial cells.

Efficient snailase-based production of mogrol from Luo Han Guo extract in an aqueous-organic system.

To solve the insufficient availability of mogrol, an 11α-hydroxy aglycone of mogrosides in Siraitia grosvenorii, snailase was employed as the enzyme to completely deglycosylate LHG extract containing 50% mogroside V. Other commonly used glycosidases performed less efficiently. Response surface methodology was conducted to optimize the productivity of mogrol, which peaked at 74.7% in an aqueous reaction. In view of the differences in water-solubility between mogrol and LHG extract, we employed an aqueous-organic system for the snailase-catalyzed reaction. Of five tested organic solvents, toluene performed best and was relatively well tolerated by snailase. After optimization, biphasic medium containing 30% toluene (v/v) could produce a high-quality mogrol (98.1% purity) at a 0.5 L scale with a production rate of 93.2% within 20 h. This toluene-aqueous biphasic system would not only provide sufficient mogrol to construct future synthetic biology systems for the preparation of mogrosides, but also facilitate the development of mogrol-based medicines.

Enzymatic hydrolyzation of mogrosides in Luo Han Guo extract by NKA-adsorbed snailase improves its sensory profile.

Extracts of Siraitia grosvenorii (Swingle), in Chinese known as Luo Han Guo (LHG), is authorized for use as a natural sweetener. LHG is rich in mogroside V that contains five glucoses, but also contains mogroside IIIE and analogues with fewer than three glucose units that cause an unpleasant aftertaste, limiting the use of the extract. Snailase was applied here to convert mogroside V in LHG extract in favor of siamenoside I formation, the sweetest mogroside with a taste similar to sucrose. For application, snailase was immobilized by adsorption to NKA (a macroporous resin), resulting in 10.9 U per g of adsorbed protein. Reuse of the NKA-adsorbed snailase was demonstrated for four cycles, and a continuous production of improved LHG extract at a 0.5 L scale had a productivity of 68.4 g/(L⋅day). The resulting product containing over 50% siamenoside I displayed an improved taste profile with satisfying safety toward HEK293T cells.

A Combined Treatment with Berberine and Andrographis Exhibits Enhanced Anti-Cancer Activity through Suppression of DNA Replication in Colorectal Cancer.

The high morbidity and mortality associated with colorectal cancer (CRC) are largely due to the invariable development of chemoresistance to classic chemotherapies, as well as intolerance to their significant toxicity. Many pharmaceutical formulations screened from natural plant extracts offer safe, inexpensive, and multi-target therapeutic options. In this study, we demonstrated that Berberis vulgaris L. (Berberine) and Andrographis paniculata (Burm. f.) Nees (Andrographis) extracts exerted their synergistic amplified anti-cancer effects by jointly inhibiting cell viability, suppressing colony formation, and inducing cell cycle arrest. Consistent with our in-vitro findings, the amplified synergistic anti-cancer effects were also observed in subcutaneous xenograft preclinical animal models, as well as patient-derived primary tumor organoids. To explore the molecular mechanisms underlying the amplified synergistic anti-cancer effects, RNA sequencing was performed to identify candidate pathways and genes. A transcriptome analysis revealed that DNA-replication-related genes, including FEN1, MCM7, PRIM1, MCM5, POLA1, MCM4, and PCNA, may be responsible for the enhanced anticancer effects of these two natural extracts. Taken together, our data revealed the powerful enhanced synergistic anti-CRC effects of berberine and Andrographis and provide evidence for the combinational targeting of DNA-replication-related genes as a promising new strategy for the therapeutic option in the management of CRC patients.

Andrographis overcomes 5-fluorouracil-associated chemoresistance through inhibition of DKK1 in colorectal cancer.

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related deaths in the USA. 5-Fluorouracil (5FU)-based chemotherapeutic drug remains a mainstay of CRC treatment. Unfortunately, ~50-60% of patients eventually develop resistance to 5FU, leading to poor survival outcomes. Our previous work revealed that andrographis enhanced 5FU-induced anti-cancer activity, but the underlying mechanistic understanding largely remains unclear. In this study, we first established 5FU-resistant (5FUR) CRC cells and observed that combined treatment with andrographis-5FU in 5FUR cells exhibited superior effect on cell viability, proliferation, and colony formation capacity compared with individual treatments (P < 0.001). To identify key genes and pathways responsible for 5FU resistance, we analyzed genome-wide transcriptomic profiling data from CRC patients who either responded or did not respond to 5FU. Among a panel of differentially expressed genes, Dickkopf-1 (DKK1) overexpression was a critical event for 5FU resistance. Moreover, andrographis significantly downregulated 5FU-induced DKK1 overexpression, accompanied with enhanced anti-tumor effects by abrogating downstream Akt-phosphorylation. In line with in vitro findings, andrographis enhanced 5FU-induced anti-cancer activity in mice xenografts and patient-derived tumoroids (P < 0.01). In conclusion, our data provide novel evidence for andrographis-mediated reversal of 5FU resistance, highlighting its potential role as an adjunct to conventional chemotherapy in CRC.