Two New Diterpenoids from Isodon rubescens

Two new diterpenoids taibairubescensin A (1) and B (2) have been isolated from Isodon rubescens. The structures of compound 1 and 2 were elucidated as 2 beta,3 beta-diacetoxy-11 beta,13 alpha-dihydroxy-ent-kaur- 16-en-15-one (1) and 3 beta,11 beta-diacetoxy-2 beta,6 alpha-dihydroxy-ent-kaur-16-en-15-one (2) on the basis of spectroscopic analysis.

Efficacy of Rabdosia Rubescens in the Treatment of Gingivitis

This study evaluated the efficacy ofrabdosia rubescens against gingivitis and compared the therapeutic efficacy of different dosage forms of rabdosia rubescens. A multi-center, randomized, double-blind, double-simulation, positive-controlled and parallel trial was conducted. A total of 136 patients exhibiting clinical symptoms of gingivitis were enrolled. The subjects were randomly assigned to two groups： test group （n=67）, in which rabdosia rubescens drop pill （960 mg） and 4 tablets of simulation agent of rabdosia rubescen were orally given to the subjects three times a day for 5 days; and control group （n=69）, in which the subjects were administered the tablets of rabdosia rubescens （1000 mg） and 24 drop pills of simulation agent of rabdosia rubescens thrice daily for 5 days. The experimental protocols and diagnostic criteria were established by expert panel prior to the experiment. The clinical symptoms were graded according to the severity of the disease and quantified. The total scores and scores for each clinical symptom of gingivitis were assessed at baseline and on the 6th day post-treatment. The therapeutic efficacy was compared between the two groups and in each group itself before and after the treatment. The results showed that in the two groups, the subjects who were given rabdosia rubescens, drop pill or tablet, had a decrease in total scores and scores for each clinical symptom when compared with those before treatment （P〈0.01）. There was significant difference in the therapeutic efficacy between the test group and the control group with the efficacy rate being 92.54% and 79.71% respectively （P〈0.05）. It was concluded that rabdosia rubescens showed great promise in treating gingivitis. And rabdosia rubescens drop pill was more efficacious than rabdosia rubescens tablet.

Static and dynamic studies of adsorption by four macroporous resins to enrich oridonin from Rabdosia rubescens

Oridonin,one of the active ingredients in Rabdosia rubescens(R.rubescens),has been reported to induce cell apoptosis and cell cycle arrest in many cancers.Conventional extraction methods tend to result in unsatisfied enrichment and poor quality of oridonin present in a given biomass.This paper aims to evaluate the performance and separation characteristics of four different macroporous resins to arrive at the most suitable methodology for the isolation and purification of highquality oridonin.Static absorption kinetics,thermodynamic and dynamic adsorption were evaluated.HP20 was selected for further study due to its high adsorption capacity of 32 mgg 1 and desorption ratio with 98.5%.The pseudosecondorder model was considered to be the most suitable for kinetic results,and Langmuir model was chosen to better describe the absorption thermodynamics.Under optimum conditions(flow rate of 4 ml min 1,bed depth with 6 cm and initial concentration of 2.15 mg·ml^1),the effective content of oridonin increased from 33.9%to 79.1%in the dry extract with a recovery of 81%and the purity of oridonin improved from 76%to 93%.The results confirm that HP20 provides an efficient method to purify most oridonin from R.rubescens.

Effect of rabdosia rubescens combined with new assistant chemotherapy on serum CA199, CEA, CA15-3 and T lymphocyte subsets in patients with breast cancer

Objective:To study the effects of Rabdosia rubescens combined with neoadjuvant chemotherapy on serum CA199, CEA, CA15-3 levels and T lymphocyte subsets in patients with breast cancer.Methods: A total of 70 patients with breast cancer in our hospital were enrolled as the subjects of this study. The subjects were divided into control group (n=35) and treatment group (n=35) randomly. Patients in the control group were treated with new assistant chemotherapy, while those who were in the treatment group were treated with rabdosia rubescens combined with new assistant chemotherapy. The two groups of patients were treated for 3 periods. The serum CA199, CEA, CA15-3 levels and peripheral blood CD4+, CD8+, CD4+/CD8+ cells of the two groups before and after treatment were compared.Results:There were no significantly differences among the serum CA199, CEA, CA15-3 levels and peripheral blood CD4+, CD8+, CD4+/CD8+ cells of the two groups before treatment. The serum CA199, CEA and CA15-3 levels of the two groups after treatment were significantly lower than those before treatment, besides, the serum CA199, CEA and CA15-3 levels of the treatment group were significantly lower than those of the control group. The peripheral blood CD4+, CD4+/CD8+ cells of the control group after treatment were significantly lower than before treatment, and the peripheral blood CD4+, CD4+/CD8+ cells of the treatment group after treatment were significantly higher than those of the control group.Conclusion:Rabdosia rubescens combined with new assistant chemotherapycan can significantly reduce the serum CA199, CEA and CA15-3 levels, and improve peripheral blood CD4+, CD8+, CD4+/CD8+ levels of patients with breast cancer. It is worthy of clinical application.

A chromosome-level genome assembly reveals that tandem-duplicated CYP706V oxidase genes control oridonin biosynthesis in the shoot apex of Isodon rubescens

The ent-kaurenoids(e.g.,oridonin and enmein)from the Isodon genus(Lamiaceae)are one class of diterpenoids with rich structural diversity and intriguing pharmaceutical activity.In contrast to the well-established gibberellin pathway,oxidative modifications diversifying the ent-kaurene skeleton in Isodon have remained undetermined for half a century.Here we report a chromosome-level genome assembly of I.rubescens,a well-recognized oridonin producer long favored by Asian people as a traditional herb with antitumor effects.The shoot apex was confirmed to be the actual region actively producing ent-kaurene diterpenoids.Through comparative genomics and phylogenetic analyses,we discovered a cluster of tandem-duplicated CYP706V oxygenase-encoding genes located on an ancient genomic block widely distributed in eudicots,whereas almost exclusively emerged in Isodon plants.In the shoot apex,IrCYP706V2 and IrCYP706V7 oxidized the ent-kaurene core in the initial stage of oridonin biosynthesis.Loss of CYP706Vs in other Lamiaceae plants offered an explanation for the specific kaurenoid production in Isodon plants.Moreover,we found that the Isodon genomes encode multiple diterpenoid synthases that are potentially involved in generating diterpenoid diversity.These findings provided new insights into the evolution of the lineage-specific diterpenoid pathway and laid a foundation for improving production of bioactive ent-kaurene-type diterpenoids by molecular breeding and synthetic biology approaches.

A New Asymmetric ent-Kauranoid Dimer from Rabdosia rubescens

Objective To study the ent-kaurane diterpenoids from Rabdosia rubescens. Methods The compounds were isolated by chromatographies and their structures were identified by spectral analyses. Results Four compounds were isolated, and they were identified as bisrubescensin E (1), 2α,3α,24-trihydroxyurs-12-en-28-oic acid (2), 2α,3α,24-trihydroxyurs-12,20-(30)-dien-28-oic acid (3), and 6,7-dihydroxycoumarin (4). Conclusion Compound 1 is a new asymmetric ent-kauranoid dimer. Compound 2 is isolated from the plant for the first time. Compounds 3 and 4 are isolated from the plants of Rabdosia (Bl.) Hassk for the first time.

冬凌草生物学研究进展

冬凌草(Rabdosia rubescens)是唇形科香茶菜属一种抗肿瘤药用植物,二萜类主要成分冬凌草甲素是其主要的活性物质。对冬凌草的生物学特性、分布、遗传多样性、冬凌草甲素及其抗癌活性、冬凌草甲素生物合成路径及其二萜类合酶、冬凌草的转录组等研究方面进行了综述,为冬凌草种质资源的合理开发利用及其相关的生物分子机制进一步发现奠定基础。

冬凌草水提取液对小麦花粉育性的影响

为了了解冬凌草[Rabdosia rubescens(Hemsl.)Hara.]对小麦(Triticum aestivumL.)花粉育性的影响,以常规小麦品种周麦18为材料,在小麦幼穗和花药发育过程中进行冬凌草水提取液的母液、2倍、3倍和4倍稀释液喷施处理,对花粉育性进行了观测,对花粉不育率和自交结实率进行了统计分析。结果表明,经冬凌草水提取液处理的周麦18,其花粉育性下降,花粉不育率上升,自交结实率下降,且随冬凌草水提取液稀释倍数的下降其效应增强,在冬凌草水提取液2倍稀释液和母液处理条件下,周麦18花粉不育率为低不育和半不育水平,自交结实率明显下降,以冬凌草水提取液母液处理效应最强。表明冬凌草水提取液对小麦化学杀雄具有积极的作用。

基于数量化理论Ⅰ的冬凌草叶中铅含量预测

目的:利用数量化理论方法筛选影响冬凌草Pb含量的关键因子,为冬凌草Pb污染水平预测及调控提供依据。方法:冬凌草Pb质量分数采用等离子发射光谱法测定,生态环境因子为样地调查实测和收集产地环境监测资料相结合,采用数量化方法 I拟合曲线分析。结果:经多因子筛选,确定影响冬凌草铅含量(Y)的贡献值最大的关键因子分别为:土壤Pb含量(X1),降水p H值(X6),污染源(X3),公路距离(X4)。结论:建立的冬凌草铅含量预测模型,可为冬凌草药源铅污染程度科学评估和有效防控提供依据。

Identification of ferroptosis as a novel mechanism for antitumor activity of natural product derivative a2 in gastric cancer

Ferroptosis is a type of cell death accompanied by iron-dependent lipid peroxidation,thus stimulating ferroptosis may be a potential strategy for treating gastric cancer,therapeutic agents against which are urgently required.Jiyuan oridonin A(JDA) is a natural compound isolated from Jiyuan Rabdosia rubescens with anti-tumor activity,unclear anti-tumor mechanisms and limited water solubility hamper its clinical application.Here,we showed a2,a new JDA derivative,inhibited the growth of gastric cancer cells.Subsequently,we discovered for the first time that a2 induced ferroptosis.Importantly,compound a2 decreased GPX4 expression and overexpressing GPX4 antagonized the anti-proliferative activity of a2.Furthermore,we demonstrated that a2 caused ferrous iron accumulation through the autophagy pathway,prevention of which rescued a2 induced ferrous iron elevation and cell growth inhibition.Moreover,a2 exhibited more potent anti-cancer activity than 5-fluorouracil in gastric canc er cell line-derived xenograft mice models.Patient-derived tumor xenograft models from different patients displayed varied sensitivity to a2,and GPX4 downregulation indicated the sensitivity of tumors to a2.Finally,a2 exhibited well pharmacokinetic characteristic s.Overall,our data suggest that inducing ferroptosis is the major mechanism mediating anti-tumor activity of a2,and a2 will hopefully serve as a promising compound for gastric cancer treatment.