Integrated metabolome and transcriptome analyses reveal the molecular mechanism underlying dynamic metabolic processes during taproot development of Panax notoginseng.

BACKGROUND: Panax notoginseng (Burk) F. H. Chen is one of the most famous Chinese traditional medicinal plants. The taproot is the main organ producing triterpenoid saponins, and its development is directly linked to the quality and yield of the harvested P. notoginseng. However, the mechanisms underlying the dynamic metabolic changes occurring during taproot development of P. notoginseng are unknown. RESULTS: We carried out metabolomic and transcriptomic analyses to investigate metabolites and gene expression during the development of P. notoginseng taproots. The differentially accumulated metabolites included amino acids and derivatives, nucleotides and derivatives, and lipids in 1-year-old taproots, flavonoids and terpenoids in 2- and 3-year-old taproots, and phenolic acids in 3-year-old taproots. The differentially expressed genes (DEGs) are related to phenylpropanoid biosynthesis, metabolic pathway and biosynthesis of secondary metabolites at all three developmental stages. Integrative analysis revealed that the phenylpropanoid biosynthesis pathway was involved in not only the development of but also metabolic changes in P. notoginseng taproots. Moreover, significant accumulation of triterpenoid saponins in 2- and 3-year-old taproots was highly correlated with the up-regulated expression of cytochrome P450s and uridine diphosphate-dependent glycosyltransferases genes. Additionally, a gene encoding RNase-like major storage protein was identified to play a dual role in the development of P. notoginseng taproots and their triterpenoid saponins synthesis. CONCLUSIONS: These results elucidate the molecular mechanism underlying the accumulation of and change relationship between primary and secondary metabolites in P. notoginseng taproots, and provide a basis for the quality control and genetic improvement of P. notoginseng.

Biosynthetic pathway of prescription bergenin from Bergenia purpurascens and Ardisia japonica.

Bergenin is a typical carbon glycoside and the primary active ingredient in antitussive drugs widely prescribed for central cough inhibition in China. The bergenin extraction industry relies on the medicinal plant species Bergenia purpurascens and Ardisia japonica as their resources. However, the bergenin biosynthetic pathway in plants remains elusive. In this study, we functionally characterized a shikimate dehydrogenase (SDH), two O-methyltransferases (OMTs), and a C-glycosyltransferase (CGT) involved in bergenin synthesis through bioinformatics analysis, heterologous expression, and enzymatic characterization. We found that BpSDH2 catalyzes the two-step dehydrogenation process of shikimic acid to form gallic acid (GA). BpOMT1 and AjOMT1 facilitate the methylation reaction at the 4-OH position of GA, resulting in the formation of 4-O-methyl gallic acid (4-O-Me-GA). AjCGT1 transfers a glucose moiety to C-2 to generate 2-Glucosyl-4-O-methyl gallic acid (2-Glucosyl-4-O-Me-GA). Bergenin production ultimately occurs in acidic conditions or via dehydration catalyzed by plant dehydratases following a ring-closure reaction. This study for the first time uncovered the biosynthetic pathway of bergenin, paving the way to rational production of bergenin in cell factories via synthetic biology strategies.

Role of NADPH oxidase in total salvianolic acid injection attenuating ischemia-reperfusion impaired cerebral microcirculation and neurons: implication of AMPK/Akt/PKC.

OBJECTIVE: TSI is a new drug derived from Chinese medicine for treatment of ischemic stroke in China. The aim of this study was to verify the therapeutic effect of TSI in a rat model of MCAO, and further explore the mechanism for its effect. METHODS: Male Sprague-Dawley rats were subjected to right MCAO for 60 minutes followed by reperfusion. TSI (1.67 mg/kg) was administrated before reperfusion via femoral vein injection. Twenty-four hours after reperfusion, the fluorescence intensity of DHR 123 in, leukocyte adhesion to and albumin leakage from the cerebral venules were observed. Neurological scores, TTC staining, brain water content, Nissl staining, TUNEL staining, and MDA content were assessed. Bcl-2/Bax, cleaved caspase-3, NADPH oxidase subunits p47(phox)/p67(phox)/gp91(phox), and AMPK/Akt/PKC were analyzed by Western blot. RESULTS: TSI attenuated I/R-induced microcirculatory disturbance and neuron damage, activated AMPK, inhibited NADPH oxidase subunits membrane translocation, suppressed Akt phosphorylation, and PKC translocation. CONCLUSIONS: TSI attenuates I/R-induced brain injury in rats, supporting its clinic use for treatment of acute ischemic stroke. The role of TSI may benefit from its antioxidant activity, which is most likely implemented via inactivation of NADPH oxidase through a signaling pathway implicating AMPK/Akt/PKC.

[Effects of warming needle moxibustion on improvement of gastrointestinal and immune function in patients with postoperation of colorectal cancer].

OBJECTIVE: To verify the clinical therapeutic effect of warming needle moxibustion on improvement of the gastrointestinal and immune function in patients with postoperation of colorectal cancer. METHODS: One hundred and five patients with postoperation of colorectal cancer were randomly divided into an acupuncture and moxibustion group, a Chinese medicine group and a routine treatment group, 35 cases in each group. They were all treated with gastrointestinal decompression and fluid replacement after operation. The acupuncture and moxibustion group was also treated with warming needle moxibustion on the 1st day after operation, and Zusanli (ST 36), Shangjuxu (ST 37) and Xiajuxu (ST 39) etc. were selected, once a day for 10 days, and the Chinese medicine group with Simo Decoction oral solution, three times daily for 10 days. The gastrointestinal function, peripheral blood components and changes of T lymphocyte and NK cells in postoperative patients were observed. RESULTS: The time of the first bowel sound, exhaust and defecation in the acupuncture and moxibustion group were all shorter than those in the Chinese medicine group and the routine treatment group (P<0.05, P<0.01). On the 10th day after operation, the percentages distribution of lymphocyte and neutrophil in the acupuncture and moxibustion group were better than those in the Chinese medicine group and the routine treatment group (all P<0.05). The acupuncture and moxibustion group was also superior to the Chinese medicine group and the routine treatment group in improving the subgroup of T lymphocyte, NK cells and the digestive system symptoms (all P<0.05). CONCLUSION: Warming needle moxibustion has a good therapeutic effect on gastrointestinal function and can regulate bidirectionally peripheral blood lymphocyte and neutrophile granulocyte and improve the T lymphocyte subgroup and NK cells so as to promote the recovery of immune function in patients with colorectal cancer after operation.