Baicalin

The pharmacological properties of the dried root of Scutellaria baicalensis Georgi, a Chinese medicinal herb, include antioxidant, antibacterial, and antiviral effects. In S. baicalensis quality assessment, concentrations of baicalin, wogonoside, baicalein, and wogonin in the root are crucial. Drought stress commonly affects the biomass and build-up of active compounds in medicinal sections of medicinal plants and thus their quality. The molecular mechanisms underlying the response of S. baicalensis to drought stress remain unexplored. To delve into the impacts of drought stress on the growth and metabolic processes of S. baicalensis, as well as to unravel the underlying molecular mechanisms. We found prolonged and intensified drought treatment causes an initial surge in its fresh weight, plant height, and stem diameter followed by a gradual slowdown, while malondialdehyde (MDA) content rises; while the fresh weight, length, superoxide dismutase (SOD), and catalase (CAT) activities peak before declining, and the root's diameter continuously narrows. In this study, flavonoid index ingredient levels in S. baicalensis initially decreased, then rose as the drought duration extended, followed by a notable post-rehydration increase in baicalin, wogonoside, and baicalein content and decrease in levels of wogonin and oroxylin A. Transcriptome sequencing and KEGG analysis revealed a significant enrichment of DEGs involved in phenylpropanoid biosynthesis and plant hormone signal transduction pathways. The expression levels of SbPAL, SbCCL, Sb4CL, SbCHI, SbFNSII, SbF6H, and SbUGT genes in the flavonoid biosynthetic pathway and PYR/PYL, PP2C, ABF, and SnRK2 genes in the abscisic acid signal transduction pathway were significantly changed. Drought responsive SbWRKY34 was selected for the subsequent investigation. SbWRKY34 showed the highest level in stems, and the encoding protein was localized in the nucleus. Overexpression of SbWRKY34 in Arabidopsis thaliana (OE-SbWRKY34 lines) resulted in increased sensitivity to drought stress, with considerably reduced MDA content and elevated SOD and CAT activities. Concurrently, the expression levels of AtCAT3, AtDREB, AtRD22, AtRD29A, and AtRD29B were significantly reduced in these lines, suggesting that SbWRKY34 functions to negatively regulate drought resistance in A. thaliana.

Chronic pancreatitis (CP), a syndrome characterized by inflammatory fibrosis, can impair both the internal and external secretory functions of the pancreas. The global incidence of this disease is gradually increasing. However, the exact pathogenesis remains unclear, resulting in a lack of targeted clinical therapies. According to the principles of traditional Chinese medicine, CP can be attributed to Shaoyang and Yangming syndromes, which manifest as abdominal pain and hypochondriac distension. Dachaihu Decoction (DCHD) is a classic formula from the "Treatise on Febrile and Miscellaneous Disease." It is frequently prescribed for conditions associated with combined Shaoyang and Yangming syndromes. However, the specific mechanisms by which DCHD prevents and treats CP remain unclear and require further investigation.

Using a holistic methodology, including network pharmacology, molecular docking, transcriptomic profiling, and animal experimentation, we explored the potential therapeutic mechanisms of DCHD in CP.

In a mouse model, caerulein was used to induce CP, and DCHD was administered via gastric lavage to assess its therapeutic effect on pancreatic injury caused by caerulein-induced CP. Subsequently, pancreatic tissues were collected for transcriptomic analysis. Screening of DCHD-active ingredient-target pathways for CP treatment was conducted using network pharmacology and further preliminary validation was performed using molecular docking techniques. Additionally, in vivo and in vitro validation was conducted using animal and cells experiments based on the predicted results.

Our findings suggest that DCHD ameliorates pancreatic acinar cell injury, pancreatic inflammation, and fibrosis in mice with CP. Network pharmacology identified 385 potential targets of DCHD associated with CP. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the therapeutic effect of DCHD on CP may be linked to the mitogen-activated protein kinase (MAPK) signaling pathway. Transcriptomic data supported this finding, as it confirmed that DCHD inhibited the pancreatic MAPK signaling pathway in CP. Molecular docking studies further revealed that the top ten active components of DCHD exhibited strong docking activity with key molecules within the MAPK signaling pathway. Finally, animal experiments confirmed that DCHD effectively reduced the phosphorylation of P38, Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) in pancreatic tissues. In addition, the expression of p-P38, p-JNK, and p-ERK was reduced in pancreatic stellate cells and macrophages in the DCHD group. We further treated CP mice, human pancreatic stellate cell line (hPSCs), and macrophage cell line RAW264.7 with the active component baicalin from DCHD, and found that baicalin effectively reduced pancreatic damage in CP. Additionally, the expression of key proteins in the MAPK signaling pathway was significantly decreased in both hPSCs and RAW264.7.

In summary, DCHD plays an important role in the treatment of chronic pancreatitis, and it may become a promising drug against the progression of CP. The role of DCHD in alleviating pancreatic inflammatory cell infiltration and fibrosis may be related to the regulation of the MAPK signaling pathway.