Six new abietane diterpenoids (1-6) and five undescribed iridoids (7-11) have been isolated from the aerial parts of Caryopteris mongolica. The intricate structural characterization of these compounds was meticulously undertaken using an array of advanced spectroscopic techniques. This process was further enhanced by the application of DP4+ probability analyses and electronic circular dichroism (ECD) calculations. Following isolation and structural elucidation, the cytotoxicity of these compounds was evaluated. Among them, compound 3 stood out, displaying significant cytotoxic activity against HeLa cells with an IC₅₀ value of 7.83 ± 1.28 μmol·L^-1. Additionally, compounds 1, 2, 4, 9, and 10 manifested moderate cytotoxic effects on specific cell lines, with IC₅₀ values ranging from 11.7 to 20.9 μmol·L^-1.
Humans ; Abietanes/chemistry* ; HeLa Cells ; Lamiaceae/chemistry* ; Circular Dichroism ; Diterpenes/chemistry* ; Molecular Structure

A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora, resulting in the characterization of five new 3, 4-seco-isopimarane (1-5) and one new 3, 4-seco-pimarane diterpenoid (6), together with four known compounds. The structures of the new compounds were fully elucidated by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and time-dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra, and DFT calculations for NMR chemical shifts and optical rotations.
Abietanes/isolation & purification* ; Callicarpa/chemistry* ; Diterpenes/isolation & purification* ; Molecular Structure ; Phytochemicals/isolation & purification* ; Plant Leaves

Dangefentong Capsules is a new traditional Chinese medicine preparation for the treatment of diabetic peripheral neuropathy. It is based on the Salviae Miltiorrhizae Radix et Rhizoma-Puerariae Lobatae Radix herb pair with salvianolic acids, tanshinones and pueraria flavonoids as main components. Studying the chemical composition in vivo of Dangefentong Capsules and its metabolites is of great significance for making clear its pharmacodynamic material basis and the action mechanism. The UHPLC-Q/Orbitrap-MS/MS was applied to rapidly analyze the metabolites and metabolic pathways of Dangefentong Capsules in Beagle dogs after gavage. Eclipse plus C_(18) column(2.1 mm×50 mm, 1.8 μm) was used, and gradient elution was performed with 0.1% formic acid aqueous solution(A)-formic acid acetonitrile solution(B). A heated electrospray ion source(HESI) was employed. The scanning mode was set as the positive and negative ion mode, and the mass scanning range was m/z 100-1 000. The plasma, urine and feces samples were collected after male Beagle dogs were administered with Dangefentong Capsules. The prototype components and metabolites were identified by UHPLC-Q/Orbitrap-MS/MS analysis combined with reference substances and references. The results showed that 107 chemical components were identified, including 58 prototype components and 49 metabolites. The identified prototype components included 42 components from Salviae Miltiorrhizae Radix et Rhizoma and 16 components from Puerariae Lobatae Radix. The metabolites consist of 21 and 28 metabolites of Salviae Miltiorrhizae Radix et Rhizoma and Puerariae Lobatae Radix, respectively. They are mainly derived from the methylation, hydroxylation, sulfation and glucuronidation of salvianolic acids, tanshinones and pueraria flavonoids. This research rapi-dly analyzes the chemical components in vivo of Beagle dogs administered with Dangefentong Capsules, laying a basis for illustrating the pharmacodynamic material basis and mechanism of Dangefentong Capsules.
Abietanes ; Acetonitriles ; Alkenes ; Animals ; Capsules ; Chromatography, High Pressure Liquid/methods* ; Dogs ; Drugs, Chinese Herbal/chemistry* ; Flavonoids ; Formates ; Male ; Polyphenols ; Pueraria ; Tandem Mass Spectrometry

Tanshinone IIA is a pharmacologically active compound isolated from Danshen (Salvia miltiorrhiza), a traditional Chinese herbal medicine for the management of cardiac diseases and other disorders. But its underlying molecular mechanisms of action are still unclear. The present investigation utilized a data mining approach based on network pharmacology to uncover the potential protein targets of Tanshinone IIA. Network pharmacology, an integrated multidisciplinary study, incorporates systems biology, network analysis, connectivity, redundancy, and pleiotropy, providing powerful new tools and insights into elucidating the fine details of drug-target interactions. In the present study, two separate drug-target networks for Tanshinone IIA were constructed using the Agilent Literature Search (ALS) and STITCH (search tool for interactions of chemicals) methods. Analysis of the ALS-constructed network revealed a target network with a scale-free topology and five top nodes (protein targets) corresponding to Fos, Jun, Src, phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA), and mitogen-activated protein kinase kinase 1 (MAP2K1), whereas analysis of the STITCH-constructed network revealed three top nodes corresponding to cytochrome P450 3A4 (CYP3A4), cytochrome P450 A1 (CYP1A1), and nuclear factor kappa B1 (NFκB1). The discrepancies were probably due to the differences in the divergent computer mining tools and databases employed by the two methods. However, it is conceivable that all eight proteins mediate important biological functions of Tanshinone IIA, contributing to its overall drug-target network. In conclusion, the current results may assist in developing a comprehensive understanding of the molecular mechanisms and signaling pathways of in a simple, compact, and visual manner.
Abietanes ; pharmacology ; therapeutic use ; Data Mining ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Diseases ; drug therapy ; Humans ; Pharmacology ; Phytotherapy ; Proteins ; metabolism ; Salvia miltiorrhiza ; chemistry

AIM: This study was designed to evaluate the anti-cancer actions of tanshinone I and tanshinone IIA, and six derivatives of tanshinone IIA on normal and cancerous colon cells. Structure activity relationship (SAR) analysis was conducted to delineate the significance of the structural modifications of tanshinones for improved anti-cancer action. METHOD: Tanshinone derivatives were designed and synthesized according to the literature. The cytotoxicity of different compounds on colon cancer cells was determined by the MTT assay. Apoptotic activity of the tanshinones was measured by flow cytometry (FCM). RESULTS: Tanshinone I and tanshinone IIA both exhibited significant cytotoxicity on colon cancer cells. They are more effective in p53(+/+) colon cancer cell line. It was also noted that the anti-cancer activity of tanshinone I was more potent and selective. Two of the derivatives of tanshinone IIA (N1 and N2) also exhibited cytotoxicity on colon cancer cells. CONCLUSION The anti-colon cancer activity of tanshinone I was more potent and selective than tanshinone IIA, and is p53 dependent. The derivatives obtained by structural modifications of tanshinone IIA exhibited lower cytotoxicity on both normal and colon cancer cells. From steric and electronic characteristics point of view, it was concluded that structural modifications of ring A and furan or dihydrofuran ring D on the basic structure of tanshinones influences the activity. An increase of the delocalization of the A and B rings could enhance the cytotoxicity of such compounds, while a non-planar and small sized D ring region would provide improved anti-cancer activity.
Abietanes ; chemistry ; pharmacology ; therapeutic use ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Cell Line ; Colon ; drug effects ; Colonic Neoplasms ; drug therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; therapeutic use ; HCT116 Cells ; HT29 Cells ; Humans ; Phytotherapy ; Salvia miltiorrhiza ; chemistry ; Structure-Activity Relationship

Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC 120 nmol·L) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA.
Abietanes ; administration & dosage ; chemical synthesis ; chemistry ; Analgesics ; administration & dosage ; chemical synthesis ; chemistry ; Animals ; Chronic Pain ; drug therapy ; enzymology ; Drug Evaluation, Preclinical ; Enzyme Inhibitors ; administration & dosage ; chemical synthesis ; chemistry ; Female ; Humans ; Male ; Mice ; Mice, Inbred ICR ; Monoacylglycerol Lipases ; antagonists & inhibitors ; metabolism ; Structure-Activity Relationship

Cisplatin and other platinum-based drugs are used frequently for treatment of lung cancer. However, their clinical performance are usually limited by drug resistance or toxic effects. Carnosic acid, a polyphenolic diterpene isolated from Rosemary (Rosemarinus officinalis), has been reported to have several pharmacological and biological activities. In the present study, the combination effect of cisplatin plus carnosic acid on mouse LLC (Lewis lung cancer) xenografts and possible underlying mechanism of action were examined. LLC-bearing mice were treated with intraperitoneal injection with cisplatin, oral gavage with carnosic acid, or combination with cisplatin and carnosic acid, respectively. Combination of carnosic acid and cisplatin yielded significantly better anti-growth and pro-apoptotic effects on LLC xenografts than drugs alone. Mechanistic study showed that carnosic acid treatment boosted the function of CD8 T cells as evidenced by higher IFN-γ secretion and higher expression of FasL, perforin as well as granzyme B. In the meantime, the proportion of MDSC (myeloid-derived suppressor cells) in tumor tissues were reduced by carnosic acid treatment and the mRNA levels of iNOS2, Arg-1, and MMP9, which are the functional markers for MDSC, were reduced. In conclusion, our study proved that the functional suppression of MDSC by carnosic acid promoted the lethality of CD8 T cells, which contributed to the enhancement of anti-lung cancer effect of cisplatin.
Abietanes ; administration & dosage ; Animals ; Antineoplastic Agents ; administration & dosage ; CD8-Positive T-Lymphocytes ; drug effects ; immunology ; Carcinoma, Lewis Lung ; drug therapy ; genetics ; immunology ; Cell Line, Tumor ; Cisplatin ; administration & dosage ; Drug Synergism ; Humans ; Interferon-gamma ; genetics ; immunology ; Lung Neoplasms ; drug therapy ; genetics ; immunology ; Matrix Metalloproteinase 9 ; genetics ; Mice ; Mice, Inbred C57BL ; Myeloid-Derived Suppressor Cells ; drug effects ; immunology ; Plant Extracts ; administration & dosage ; Rosmarinus ; chemistry