Ethnopharmacological relevance: Crebanine (Cre) and Stephanine (Step) are isoquinoline aporphine-type alkaloids that are extracted from Stephania yunnanenses H. S. Lo. Plants of the Stephania genus are often used for treatment of stomach pain, abdominal pain, and rheumatoid arthritis. Both Cre and Step exhibit strong activities but are also associated with a certain level of toxicity, 10,11-dibrominecrebanine (2Br-Cre) is a bromine-modified derivative of Cre that we prepared and tested in order to reduce toxicity and enhance efficacy.Aim of this study: To investigate the anti-inflammatory and analgesic effects of 2Br-Cre and Step based on previous research findings and explore the specific biological mechanisms involved.Materials and methods: The anti-inflammatory and analgesic effects of 2Br-Cre and Step were investigated using a range of experimental models, including xylene-induced ear edema, carrageenan-induced pleurisy, carrageenan-induced paw edema, the hot-plate test, the naloxone antagonism test and the acetic acid writhing test. A model of chronic constriction injury (CCI) of the sciatic nerve was also established to investigate therapeutic effects. A RAW264.7 cell model was established using lipopolysaccharide (LPS) to estimate the effects of these compounds on cytokines levels.Results: 2Br-Cre and step significantly inhibited ear edema, paw edema and presented anti-inflammatory activity in the pleurisy model by inhibiting leukocyte migration and nitric oxide (NO) production, and by reducing the levels of PGE2. 2Br-Cre and Step significantly increased the pain threshold of mice subjected to heat stimulation; the effect was blocked by naloxone, thus suggesting that the analgesic effects of 2Br-Cre and Step were mediated by opioid receptors. 2Br-Cre and Step inhibited the frequency of writhing and prolonged the latency of writhing, and reduced the abnormal increase in the levels of BDNF in the serum and brain, thus alleviating the pain caused by CCI. In addition, 2Br-Cre and Step significantly inhibited the production of several inflammatory cytokines (IL-6, IL-1β and TNF-α) by LPS-induced RAW264.7 macrophages (p < .01).Conclusion: 2Br-Cre and Step exerted remarkable anti-inflammatory and analgesic effects. As a structural modification of Cre, 2Br-Cre retains the anti-inflammatory and analgesic activity of Cre but with better efficacy. Consequently, 2Br-Cre should be investigated further as a lead compound for analgesia.

Salvia miltiorrhiza Bunge (Danshen) is an important traditional Chinese medicine herb. This study aimed to investigate the drought-responsive metabolic profiling in S. miltiorrhiza using gas chromatography time-of-flight mass spectrometry (GC-TOFMS) analysis. Fifty day-old S. miltiorrhiza seedlings were treated with two (moderate drought, MD) and four weeks (high drought, HD) of withholding water. The S. miltiorrhiza leaf and root samples were prepared for the GC-TOFMS analysis. Differential metabolites with substantial changes in content in S. miltiorrhiza leaf and root were identified using multivariate and univariate statistics. A total of 178 and 157 annotated metabolites were detected in S. miltiorrhiza leaf and root, respectively. Multivariate analysis showed that significantly discriminant metabolites in S. miltiorrhiza leaf by drought were associated with “galactose metabolism” and “citrate cycle”. In addition, the significantly discriminant metabolites in S. miltiorrhiza root were associated with “starch and sucrose metabolism”. Univariate statistics showed that the content of succinic acid, d-glucose, and oxoglutaric acid in S. miltiorrhiza leaf was increased by drought (fold change, FC > 1.5). Allose, d-xylose, melibiose, mannose, sorbitol, quinic acid, sinigrin, and taurine in S. miltiorrhiza root were decreased by drought (FC < 0.67). There were different metabolic profiles between S. miltiorrhiza leaf and root. However, the influence of drought stress on the pharmacological value and accumulation of bioactive constituents in S. miltiorrhiza should be further investigated.

Drought stress is a major constraint to the quality and production of Salvia miltiorrhiza Bunge (Danshen). This study aimed to investigate the posttranslational molecular mechanisms in S. miltiorrhiza leaves in response to drought stress using quantitative phosphoproteomics analysis. S. miltiorrhiza plants were stressed by withholding water for two (moderate drought stress) and four weeks (high drought stress). Leaf samples were prepared with tandem mass tag labeling. Liquid chromatography-tandem mass spectrometry was performed for the quantitative phosphoproteomics. Bioinformatics methods were used to identify the phosphosites and phosphoproteins that had significantly changed phosphorylation levels upon drought stresses. A total of 119 common phosphoproteins were significantly changed by both high and moderate drought stresses. The phosphorylation levels of proteins related to protein processing, photosynthesis, RNA binding, and splicing were significantly changed upon high drought, not moderate drought. Additionally, we identified that the Ser phosphorylation levels of most proteins related to terpene metabolism and RNA splicing were regulated by drought stresses. The Ser and Thr phosphorylation levels of energy metabolism proteins (including FBA2/8, PPC4, and PPCC) and heat shock proteins (including HSP70 and HSP90) were upregulated by drought stresses. Our study showed the posttranscriptional mechanisms in S. miltiorrhiza leaves in response to drought stress.

Potassium application can effectively mitigate the effects of drought stress on plant growth, and few studies have reported its application to the medicinal plant Salvia miltiorrhiza (S. miltiorrhiza). Four experimental treatments were used, including a control (Z1K0), non-drought potassium application (Z1K3), drought treatments (Z2K0), and drought-stress potassium application (Z2K3). The findings revealed that, in contrast to Z2K0, Z2K3 promoted the absorption of potassium in S. miltiorrhiza, elicited the aggregation of osmoregulatory compounds such as soluble protein and proline, and mitigated membrane impairment as a defense against the deleterious consequences of drought stress. Additionally, we extended our investigation to encompass comprehensive metabolomics analysis of the roots. Interestingly, subsequent root metabolomics analyses demonstrated that the drought application of potassium not only significantly reduced the amino acid content, but also increased the amount of terpenoids and phenolic acids in the roots. Nonetheless, the application of a particular amount of K under moderate drought conditions promoted the growth and yield of S. miltiorrhiza, but proved to be detrimental to its active ingredients. Indeed, the findings of this study offer valuable insights and recommendations for the application of potassium to mitigate the impact of drought stress in S. miltiorrhiza and other medicinal plants.

Zeugodacus tau Walker (Diptera: Tephritidae) is a quarantine pest of cucurbit crops in China. In recent years, the damage it has caused to Trichosanthes kirilowii (Cucurbitales: Cucurbitaceae) has increased, but evidence for host adaptation and population growth on this plant remains limited. We investigated the suitability of T. kirilowii as a host plant for Z. tau, compared with the known suitable host Cucurbita moschata, by examining adult olfactory preference, oviposition choice, and demographic performance using an age–stage, two-sex life table. Females preferred T. kirilowii significantly more than C. moschata in cases of both peeled and unpeeled fruits, whereas males showed no significant difference. Oviposition was also higher on T. kirilowii and further increased on peeled fruit. Developmental duration, total longevity, ovipositing days, oviposition period, and hatching rate did not differ between the two host species. However, Z. tau reared on T. kirilowii exhibited significantly shorter APOP and TPOP, along with higher fecundity and increased pupal weight. Life table parameters indicated higher intrinsic (r = 0.1028 ± 0.0040 d⁻¹) and finite rates of increase (λ = 1.1083 ± 0.0044 d⁻¹) on T. kirilowii, whereas R₀ was similar and mean generation time was shortened by 11.61 d. A 100-day projection predicted 11,980 adults from T. kirilowii compared to 1231 from C. moschata. Overall, T. kirilowii is a highly suitable host that supports the rapid population growth of Z. tau.