摘要：
Norditerpenes are considered to be a common and widely studied class of bioactive compounds in plants, exhibiting a wide array of complex and diverse structural types and originating from various sources. Based on the number of carbons, norditerpenes can be categorized into C19, C18, C17, and C16 compounds. Up to now, 557 norditerpenes and their derivatives have been found in studies published between 2010 and 2023, distributed in 51 families and 132 species, with the largest number in Lamiaceae, Euphorbiaceae, and Cephalotaxaceae. These norditerpenes display versatile biological activities, including anti-tumor, anti-inflammatory, antimicrobial, and antioxidant properties, as well as inhibitory effects against HIV and alpha-glucosidase, and can be considered as an important source of treatment for a variety of diseases that had a high commercial value. This review provides a comprehensive summary of the plant sources, chemical structures, and biological activities of norditerpenes derived from natural sources, serving as a valuable reference for further research development and application in this field.
期刊：
European Journal of Pharmacology,2024年963:176264 ISSN：0014-2999
通讯作者：
Yang, Yantao;Chen, Naihong;Liu, F;Chen, NH
作者机构：
[Ai, Qidi; Peng, Caiwang; Sun, Yang; Zhao, Fengyan; Tang, Keyan; Yang, Yantao; Chen, Naihong; Li, Hengli; Liu, Fang] Hunan Univ Chinese Med, Sch Pharm, Changsha 410208, Peoples R China.;[Ai, Qidi; Peng, Caiwang; Sun, Yang; Yang, YT; Liu, Fang; Zhao, Fengyan; Chen, NH; Tang, Keyan; Yang, Yantao; Chen, Naihong; Li, Hengli] Ctr Standardizat & Funct Engn Tradit Chinese Med H, Changsha 410208, Peoples R China.;[Peng, Caiwang; Zhao, Fengyan; Tang, Keyan; Li, Hengli; Liu, Fang] Educ Dept Hunan Prov, Key Lab Modern Res TCM, Changsha 410208, Peoples R China.;[Chen, NH; Chen, Naihong] Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China.;[Liu, Fang] Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
通讯机构：
[Yang, YT; Liu, F ; Chen, NH ; Chen, NH] C;Ctr Standardizat & Funct Engn Tradit Chinese Med H, Changsha 410208, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, Beijing 100050, Peoples R China.;Hunan Univ Chinese Med, Sch Pharm, 300 Xueshi Rd, Changsha 410208, Peoples R China.
摘要：
AIMS: Ischemic stroke is a severe cerebrovascular disease in which neuronal death continually occurs through multiple forms, including apoptosis, autophagy, pyroptosis and ferroptosis. Quercetin (QRC), as a natural flavonoid compound, has been reported to have pharmacological effects on ischemic injury accompanied by unclear anti-ferroptotic mechanisms. This study is designed to investigate the therapeutic effects of QRC against ferroptosis in ischemic stroke. MATERIALS AND METHODS: In vivo, the model of MCAO rats were used to assess the protective effect of QRC on cerebral ischemic. Additionally, we constructed oxidative stressed and ferroptotic cell models to explore the effects and mechanisms of QRC on ferroptosis. The related proteins were analysed by western blotting, immunohistochemical and immunofluorescence techniques. RESULTS: The experiments demonstrated that QRC improves neurological deficits, infarct volume, and pathological features in MCAO rats, also increased the viability of HT-22cells exposed to H(2)O(2) and erastin. These results, including MDA, SOD, GSH, ROS levels and iron accumulation, indicated that QRC suppresses the generation of lipid peroxides and may involve in the regulatory of ferroptosis. Both in vitro and in vivo, QRC was found to inhibit ferroptosis by up-regulating GPX4 and FTH1, as well as down-regulating ACSL4. Furthermore, we observed that QRC enhances the nuclear translocation of Nrf2 and activates the downstream antioxidative proteins. Importantly, the effect of QRC on ferroptosis can be reversed by the Nrf2 inhibitor ML385. CONCLUSIONS: This study provides evidence that QRC has a neuroprotective effect by inhibiting ferroptosis, demonstrating the therapeutic potential for cerebral ischemic stroke.
摘要：
Objective To establish a network dynamic equilibrium constant model based on the principle of material flow balance in the supramolecular"imprinted template"theory of Buyang Huanwu Decoction(补阳还五汤)for treating ischemic stroke,and clarify the relationship between the components of Buyang Huanwu Decoction compound for treating cerebral ischemia,in order to provide a new idea for the complex system of traditional Chinese medicine(TCM)compound for treating diseases.Methods HPLC-MS/MS was used to determine the components and concentrations of Buyang Huanwu Decoction in blood to study the disturbance of the system induced by re-administration within the steady-state concentration of blood drugs.Using the mathematical model of network dynamics as the medium,20 active components were selected as nodes in the model to calculate the dynamic equilibrium constant parameters of Buyang Huanwu Decoction network.In this way,the relationship between the components of Buyang Huanwu Decoction in vivo was revealed by means of equilibrium constant matrix.Results In the topology network of equilibrium constant constructed,10 components of Buyang Huanwu Decoction had positive effects in blood,which were sorted as follows:Isoastragaloside Ⅰ＞succinic acid＞ononin＞senkyunolide H＞senkyunolide Ⅰ＞vanillin＞butylidenephthalide＞amygdalin＞oxypaeoniflorin＞methylnissolin;The other 10 components had negative effects,sorted by effect as follows:Astragaloside Ⅰ＞senkyunolide C＞ferulic acid＞hydroxysafflor yellow A＞ligustilide＞daucosterol＞senkyunolide A＞calycosin＞formononetin＞calycosin7-O-β-D-glucopyranoside.The equilibrium constants of isoastragalus Ⅰ and astragalus Ⅰ were larger.Conclusion Isoastragalus Ⅰ and astragalusⅠ have a great effect on the network among the constituent groups in the constructed topological equilibrium constant network,which may be the"blot template"of Buyang Huanwu Decoction in the treatment of ischemic stroke.
摘要：
The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer‑associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.
作者机构：
[Fangming Zhang; Hui Zheng; Tao Zheng; Pan Xu; Yao Xu; Yuxin Cao; Fan Jia; Yiqiong Zeng; Yubing Fan; Yong Yang] College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China;[Kai He] School of Pharmaceutical Science, Hunan University of Medicine, Huaihua 418000, China;[Xinwen Dai; Fengfei Hou] Hunan Fuling Engineering Technology Research Center, Huaihua 418100, China
通讯机构：
[Kai He] S;[Yong Yang] C;School of Pharmaceutical Science, Hunan University of Medicine, Huaihua 418000, China<&wdkj&>College of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
摘要：
Poria cocos (PC) is a famous traditional Chinese medicine (TCM) and a widely used healthcare ingredient, which has antiobesity, enhancing immunity and improving sleep effects. Traditionally, only water-soluble poria polysaccharide (WSP) is extracted and applied for clinical application, while insoluble polysaccharide (alkali-soluble poria polysaccharide, ASP) is discarded as herb residue. However, the whole PC has also been historically utilized as functional herbal food. Considering the beneficial role of dietary fiber and the traditional use of PC, ASP may also contribute substantially to the therapy function of PC. Compared to WSP, little attention has been paid to ASP and ASP modified product carboxymethyl poria polysaccharide (CMP) which has been used as an antitumor adjuvant drug. In this study, the oil, cholesterol, metal ions and polyphenols adsorption ability, in vitro simulated digestive and the gut microbiota fermentation characteristics of WSP, ASP and CMP were studied to evaluate the functional values of three P. cocos polysaccharides (PCPs). The results showed that all three PCPs had good adsorption capacity on cholesterol, polyphenols and metal ions (Cd2+/Zn2+/Mg2+), among which ASP showed the highest capacity than WSP and CMP. The adsorption capacity of all three PCPs on heavy metal ions (Cd2+/Zn2+) was stronger than that of non-heavy metal ions (Mg2+); The in vitro digestibility of all three PCPs was very low, but WSP was slightly higher than ASP and CMP; Moreover, the indigestible residue of all three PCPs could improve the richness and diversity of gut microbiota, among which ASP had the greatest influence. In general, ASP and CMP could significantly promote the proliferation of some probiotics and inhibit the growth of some harmful bacteria. The gut microbiota diversity of CMP was reduced, but the richness of probiotics, especially Parabacteroides distasonis was significantly enhanced compared with the ASP group, and the growth of harmful bacteria Klebsiella pneumoniae was inhibited after CMP treatment. The short-chain fatty acids (SCFAs) analysis results showed that all three PCPs could significantly promote the production of acetic acid, propionic acid and the total acid content compared with blank control group, and SCFAs producing activity was positively correlated with the proliferative capacity of probiotics. Taken together, the good adsorption characteristics and gut microbiota regulatory activity of ASP may lay foundation for its lipid-lowering and immune-improving function. Additionally, the probiotic effect of CMP and ASP indicated that except for only use the water extract of PC in clinic, CMP and ASP also can be used in healthcare to take full advantage of this valuable medicine.
期刊：
Drug Discoveries & Therapeutics,2024年18(1):34-43 ISSN：1881-7831
作者机构：
[Chen, Shanshan; Wang, Shengfeng] Department of Pharmacy, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;[Ouyang, Linqi] Department of Pharmacy, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China;[Li, Lian] Department of Information, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China;[Xiao, Yuyang] Xiangya School of Medicine, Central South University, Changsha, Hunan, China;[Wang, Shengfeng] Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China
摘要：
To get a thorough understanding of PD-1/L1 inhibitor-related hypophysitis (PD-1/L1-irH), we utilized a combination of disproportionality analysis and case analysis to comprehensively characterize the clinical features of PD-1/L1-irH. Significant signals of hypophysitis were detected for all PD-1/PD-L1 inhibitors in the FAERS (FDA Adverse Event Reporting System). As revealed by both FAERS and the case analysis, PD-1/L1-irH occurred more commonly in males, PD-1 inhibitors users and patients older than 65 years. The median onset time was 101 days in FAERS and 8 cycles in the case analysis. In the case analysis, eight late-onset PD-1/L1-irHs occurred even after a discontinuation of several months (4-15 months). As revealed in FAERS, the outcome of PD-1/L1-irH tended to be poor, generally resulting in 64.66% hospitalization and 12.59% death. Fatigue was the most prominent symptom of PD-1/L1-irH, followed by anorexia, hyponatremia, and hypotension, as revealed by the analysis of 84 cases. Meanwhile isolated adrenocorticotropic (ACTH) deficiency was particularly prevalent for PD-1/L1-irH (85.71%), while gonadal hormones or posterior pituitary hormones deficiencies were rare. Glucocorticoids were administered to almost all cases (81/84), with a physiologic or stress dosage in 61.9% of cases, and a high-dose in 26.2% of cases. Most cases (58.3%) showed a favorable tumor response before diagnosis of PD-1/L1-irH. PD-1/L1-irH may occur throughout the whole therapy period even after discontinuation. Clinicians should pay more attention to PD-1 inhibitor users, males and older patients. Early diagnosis and prompt managements are crucial for PD-1/L1-irH as its potentially life-threatening nature.
作者机构：
[Lu, Huiling; Xiao, Yifei; Li, Ya; Du, Lixin] Hunan Univ Chinese Med, Coll Pharm, Changsha, Peoples R China.;[Guo, Zhihua] Hunan Univ Chinese Med, Coll Chinese Med, Changsha, Peoples R China.;[Li, Y; Li, Ya] Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
通讯机构：
[Li, Y ] H;Hunan Univ Chinese Med, Coll Pharm, Changsha 410208, Peoples R China.
关键词：
Chuantieling gel patch;fingerprint;HPLC;network pharmacology;Q-markers
摘要：
The Chuantieling gel patch (CGP), a traditional Chinese medicine compound, is an external treatment for asthma. It has shown remarkable effectiveness in alleviating asthma-related airway hyperresponsiveness and inflammation. Nevertheless, there is currently no information available regarding the analysis of quality markers for CGP, and there is a need for further improvement in quality control research. In this study, we developed an HPLC fingerprinting method for CGP and conducted a comprehensive methodological investigation. We assessed the similarity among 10 batches of CGP, identified common peaks, and quantified the content of seven major quality markers. Furthermore, we built a network pharmacology-based 'active ingredients-targets-pathways-diseases' network to forecast the potential mechanisms of action for the primary active components in asthma treatment. Our findings demonstrated that the developed CGP fingerprinting and content determination methods were consistent and trustworthy. We verified the existence of 25 shared peaks and successfully identified 7 chromatographic peaks, including sinigrin thiocyanate, ephedrine hydrochloride, methyleugenol, imperatorin, cinnamaldehyde, emodin, and 6-gingerol, using reference standards. The network pharmacology analysis suggested that these seven active components may target proteins such as STAT3 (signal transducer and activator of transcription 3), MAPK3 (mitogen-activated protein kinase 3), and TP53 (tumor protein P53) and influence various diseases through pathways including cancer pathways, hepatitis B, and PI3K-Akt (phosphoinositide 3-kinase-protein kinase B) signaling. This study provides insight into the complex multicomponent composition of CGP, and the predictive analysis through network pharmacology sets the stage for uncovering the mechanisms responsible for the therapeutic effects of CGP.
