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Two new iridoid glycosides, 2′-O-cis-coumaroylgardoside (1), and 6′-O-caffeoylioxide (2), were isolated from the fruit of Gardenia jasminoides. The structures of these compounds were elucidated based on spectroscopic analysis (HR-ESI-MS, NMR) and chemical methods. The anti-inflammatory activities of the isolates were evaluated by measuring their inhibitory effects on PGE2 production in LPS stimulated RAW 264.7 macrophages, compounds 1 and 2 could reduce PGE2 levels in LPS-activated RAW 264.7 macrophages with IC50 values of 121.4 and 83.38 μM, respectively. [ABSTRACT FROM AUTHOR]

Cimicifuga dahurica (Turcz.) Maxim, which is also regarded as the main origin of "Shengma" in the Chinese Pharmacopoeia, has been used as a cooling and detoxification agent for thousands of years. Our previous phytochemical investigations of C. dahurica extracts (CDEs) led to the isolation of a series of 9,19‐cycloalkane triterpenoids and phenolic acids showing a potential anti‐inflammatory activity. However, the chemical profiling of CDEs and the material basis of its anti‐inflammatory effect in vivo has not been clarified. In the present study, the CDE chemical profile and prototype components in rat plasma were identified via ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry. As a result, a total of 106 components were identified or tentatively characterized in CDEs, including 54 triterpenoids, 35 phenolic acids, eight amides and nine other type constituents (39 compounds were confirmed with the reference standards). In addition, 20 prototype components (15 triterpenoids and five phenolic acids) were identified in rat plasma, which potentially related to the anti‐inflammatory effects of CDEs. Moreover, the anti‐inflammatory activities of the main prototype components were further evaluated by their inhibitory effects on the production of NO, as well as the expressions of iNOS and COX‐2 in lipopolysaccharide‐stimulated RAW264.7 cells, which indicated that 9,19‐cycloalkane triterpenoids may play an anti‐inflammatory role by down‐regulating the expression of iNOS. [ABSTRACT FROM AUTHOR]

Ten cycloart-7-ene triterpenoid glycosides, including three new compounds (1–3), were isolated from the roots of Cimicifuga dahurica. Their structures were elucidated on the basis of extensive spectroscopic analyses, chemical methods and comparison with literatures. In addition, the isolates were evaluated for their inhibitory effects on the production of NO, as well as the expressions of iNOS and COX-2 in LPS-stimulated RAW 264.7 macrophages. The results showed that compounds 3, 5, 6, 7 and 8 can reduce the release of NO in a dose-dependent manner. Mechanistically, Western blot analysis indicated that the NO inhibitory effects relied on down-regulating the expression of iNOS, and partially associated with lowering the expression of COX-2. [ABSTRACT FROM AUTHOR]

A new nitrogen-containing iridoid glycoside, named (7 R,3′R)-lonijapospiroside A (1), together with thirteen known iridoid glycosides, were isolated from the flower buds of Lonicera macranthoides. The structures of these compounds were established on the basis of spectroscopic analyses. Among them, compounds 1-4 are four diastereoisomers, and their absolute configurations were accurately established by the NOE spectra as well as comparison of their experimental and calculated ECD spectra. The anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on NO, IL-6, and TNF-α production in LPS stimulated RAW 264.7 macrophages. Compound 14 exhibited anti-inflammatory activities by inhibiting IL-6 with an IC50 value of 54.70 μM, comparable to that of the positive control (hydrocortisone, IC50: 62.6 ± 1.7 μM). [ABSTRACT FROM AUTHOR]

Jin‐hong tablets (JHTs), a well‐known traditional Chinese patent medicine (TCPM), have been effectively used for the treatment of chronic superficial gastritis (CSG). The metabolic profile of TCPMs is performed to determine their bioactive components. In this study, a five‐step strategy based on ultra‐performance liquid chromatography coupled with quadrupole time‐of‐flight tandem mass spectrometry and metabolynx™ software combined with mass defect filter technique was developed to delineate the metabolic profile of JHT in vivo. As a result, a total of 163 JHT‐related xenobiotics (38 prototypes and 125 metabolites) were identified or tentatively characterized in rat biological samples, and the phase I and II metabolism processes mainly included demethylation, hydroxylation, sulfation, and glucuronidation. In addition, after oral administration of JHT, a large amount of alkaloid‐related ingredients was detected in rat plasma samples, indicating that alkaloids may play an important role in the treatment of CSG with JHT. This study is beneficial for understanding the JHT's in vivo metabolic profiles and characteristics, which helps to reveal its in vivo effective components and provides a solid basis for further studies on its functional mechanism. [ABSTRACT FROM AUTHOR]

Oncogenic KRAS is considered a promising target for anti‐cancer therapy. However, direct pharmacological strategies targeting KRAS‐driven cancers remained unavailable. The prenyl‐binding protein PDEδ, a transporter of KRAS, has been identified as a potential target for pharmacological inhibitor by selectively binding to its prenyl‐binding pocket, impairing oncogenic KRAS signaling pathway. Here, we discovered a novel PDEδ inhibitor (E)‐N′‐((3‐(tert‐butyl)‐2‐hydroxy‐6,7,8,9‐tetrahydrodibenzo[b,dfuran‐1‐yl)methylene)‐2,4‐dihydroxybenzohydrazide(NHTD) by using a high‐throughput docking‐based virtual screening approach. In vitro and in vivo studies demonstrated that NHTD suppressed proliferation, induced apoptosis and inhibited oncogenic K‐RAS signaling pathways by disrupting KRAS‐PDEδ interaction in nonsmall cell lung cancer (NSCLC) harboring KRAS mutations. NHTD redistributed the localization of KRAS to endomembranes by targeting the prenyl‐binding pocket of PDEδ and exhibited the suppression of abnormal KRAS function. Importantly, NHTD prevented tumor growth in xenograft and KRAS mutant mouse model, which presents an effective strategy targeting KRAS‐driven cancer. What's new? Mutations in KRAS frequently are observed in cancer, resulting in aberrant signaling activity. This activity is strongly dependent on KRAS localization to the plasma membrane, a process modulated by phosphodiesterase 6 delta (PDEδ). Here, a promising PDEδ inhibitor, NHTD, was identified via analysis of interactions between PDEδ and compound libraries using an induced fit docking‐based screening approach. In KRAS‐mutant cells, NHTD disrupted KRAS‐PDEδ interaction by selectively attaching to its prenyl‐binding pocket. NHTD further reduced aberrant KRAS signaling and induced apoptosis. NHTD prevented tumor growth in mice. The findings warrant further investigation of NHTD as a potential therapy against KRAS‐driven cancer. [ABSTRACT FROM AUTHOR]

Jin-Zhen oral liquid (JZOL), a well-known traditional Chinese medicine prescription (TCMp), has extensively been used to treat acute bronchitis in children more than four hundred years in China. However, the current quality control standard of JZOL is inadequate, posing challenges for its internationalization. In this study, a Q-marker screening strategy based on multi-factor analysis was proposed to comprehensively evaluate anti-inflammatory Q-markers of Jin-Zhen oral liquid (JZOL). Firstly, the chemical profile and the pharmacokinetics properties of multiple components in JZOL were characterized by UPLC-Q/TOF-MS and UPLC-QqQ-MS. By integrating the measurable and absorbed components, twenty-two components with structures accurately defined, were selected as candidate Q-markers of JZOL. Following that, a network connecting 22 components and targets closely associated with bronchitis was established. Afterwards, a multi-factor analysis mode was developed to balance the components' multiple characteristics, and screen out the anti-inflammatory Q-markers in JZOL. Finally, the anti-inflammatory activity evaluation was conducted by LPS-induced RAW 264.7 macrophages to prove the representativeness of anti-inflammatory Q-markers in JZOL. As a result, a total of 92 components were characterized in JZOL and the pharmacokinetics properties of 11 bioactive components in vivo were further characterized. Then, an overlapping of 46 targets involved in the interactions of selected 22 candidate Q-markers and the regulation of bronchitis inflammation were collected. Subsequently, a multi-factor analysis was developed on 22 candidate anti-inflammatory Q-markers covering five factors, with the statistic KMO values of 0.645, and the P values of Bartlett's Test equal to 0.000. A total of seven ingredients (aloeemodin-8 -O - β - d -glucopyranoside, baicalin, chrysin-7- O - β - d -glucuronide, oroxylin A 7- O - β - d -glucuronide, wogonoside, chrysophanol-8 -O - β - d -glucopyranoside, and skullcapflavone II) were selected as Q-markers of JZOL, and the inhibitory effects of these candidate Q-markers on the secretion of inflammatory cytokes (NO, IL-6, IL-1β, and PGE 2) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells were evaluated and confirmed. This study not only offers a fresh approach to uncovering Q-markers in the quality control research of TCMps but also identifies the suitable anti-inflammatory Q-markers for JZOL for the first time, with the potential to serve as a reference for existing quality control standards of JZOL. [ABSTRACT FROM AUTHOR]

Lung cancer is the number one cancer in terms of both mortality and incidence. Cancer cells differ from normal cells in that they can reprogram their metabolism to support a rapid proliferation rate and alter oxidative phosphorylation processes toward lactic acid fermentation, even under aerobic conditions. Therefore, we aimed to identify new compounds that might act as pyruvate kinase M2 isoform (PKM2) activators and to investigate their anti‐cancer efficacy in non‐small‐cell lung cancer (NSCLC) cells. The molecular docking method was applied to screen PKM2 activators from our virtual natural products library. Then, compounds with promising docking scores were examined for cytotoxic effects in a panel of NSCLC cells using the MTT assay. Functional effects and therapeutic mechanisms were investigated by in vitro enzyme assays, western blotting (WB), and flow cytometry. Molecular docking showed that 0089‐0022 acts as a potential PKM2 activator by binding to the kinase pocket. An in vitro enzyme activity assay showed that 0089‐0022 is a direct PKM2 activator and that it effectively induces apoptosis in A549 and H1975 cells through inhibition of AKT phosphorylation. Our results suggest that 0089‐0022 activates PKM2 and thus is a promising anti‐cancer therapeutic candidate in NSCLC. We have identified a novel compound, 0089‐0022, targeting a critical enzyme controlling cell glycolysis process, PKM2. 0089‐0022 induces cell apoptosis through inhibition of AKT signaling pathways in both EGFR and KRAS mutant NSCLC cells. 0089‐0022 has less cytotoxic effect in lung normal epithelial cells. [ABSTRACT FROM AUTHOR]

The cover image is based on the Research Article Identification of a new pyruvate kinase M2 isoform (PKM2) activator for the treatment of non‐small‐cell lung cancer (NSCLC), by Run‐Ze Li et al., DOI: 10.1111/cbdd.13354. [ABSTRACT FROM AUTHOR]

Desmodeleganine ( 1 ), a new potential monoamine oxidase inhibitor, along with three known alkaloids, bufotenin ( 2 ), hydroxy- N , N -dimethyltryptamine N 12 -oxide ( 3 ), 2-(5-methoxy-1H-indol-3-yl)- N , and N -dimethylethylamine ( 4 ) were isolated from the leaves of Desmodium elegans . Their structures were elucidated by IR, MS, 1D and 2D NMR spectra. 1 showed strong monoamine oxidase inhibitory activity with IC 50 value of 13.92 ± 1.5 μM, when the IC 50 value of iproniazid as a standard was 6.5 ± 0.5 μM. The molecular modeling was also performed to explore the binding mode of compounds 1 , 2 at the active site of MAO-A and MAO-B. [ABSTRACT FROM AUTHOR]

• An UHPLC-MS/MS method was developed and validated for simultaneous quantitative analysis of ten sex steroid hormones in rat and mouse serum. • The method was successfully applied in XLGB-intervened OVX rats. • XLGB could not only improve the levels of E 2 , P, 17OHP and ATI, but also regulate the ratio of P to progestogen and T to androgen. • The molecular docking results showed that psoralen, isopsoralen and sweroside could activate AC on promoting steroid hormones biosynthesis. • It is the first time to evaluate the regulatory effect of kidney-tonifying TCMP on steroid hormones in ovariectomy-induced osteoporosis rat. Sex steroid hormones could directly affect the bone metabolism by regulating cell physiological functions. In female, it inevitably causes the abnormal levels of sex steroid hormones at post-menopause in vivo. Ovariectomized rats and mice are classic animal models of osteoporosis to better understand the action mechanism of anti-osteoporosis drugs. However, it is not clear whether Xian-Ling-Gu-Bao capsule (XLGB), a kidney-tonifying traditional Chinese medicine prescription, treat osteoporosis via regulating multiple sex steroid hormones. In the present study, a reliable method involving ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC/TQ-XS-MS) was developed for simultaneous quantitative analysis of ten sex steroid hormones (three estrogens, five androgens and two progestogens) in rat and mouse serum. The results of methodology were acceptable. The validated method was then successfully applied in the determination of the levels of sex steroid hormones in ovariectomy-induced osteoporosis rats, as well as drug (17β-estradiol and XLGB) intervened rats. As a result, XLGB could not only significantly increase the level of 17β-estradiol, but also improve the levels of progesterone, 17α-hydroxyprogesterone and androstenedione. Combined with molecular docking results and pharmacokinetic parameters, psoralen, isopsoralen and sweroside were considered as the key effective components of XLGB to activate adenylyl cyclase on promoting the biosynthesis of multiple sex steroid hormones. It is the first time to evaluate the regulatory effect of kidney-tonifying traditional Chinese medicine prescription on the levels of steroids in ovariectomy-induced osteoporosis rat, as well as the potential substance basis and mechanism of steroid hormone regulation. [ABSTRACT FROM AUTHOR]

Phytochemical study on rhizomes of Cimicifuga dahurica resulted in the isolation of nine new neolignan and phenylpropanoid glycosides, cimicifugasides A-E (1, 2, 7–9), cimicifugamides B-D (3 – 5), shomaside G (6) along with four known compounds (10 − 13). Their structures were identified by extensive spectroscopic analyses (1D-, 2D-NMR, MS, CD, IR, UV) and chemical methods. Their anti-inflammatory potentials were evaluated by measuring their effects on PGE 2 production of LPS-stimulated RAW264.7 cells, and compounds 12 and 13 showed moderate anti-inflammatory activities. Unlabelled Image [ABSTRACT FROM AUTHOR]

Four previously unreported sesquiterpenoid diasteromers, arteannoides U–X (1 – 4), together with one new norsesquiterpenoid 5 (arteannoide Y) and one undescribed rearranged cadinene sesquiterpenoid 6 (arteannoide Z) were obtained from the dried aerial parts of Artemisia annua (Qinghao). Notably, arteannoides U–X (1 – 4) are four stereoisomers that possess the same molecules and the same planar connectivity, but differ from each other in configuration at a certain stereocenter. Their accurate structures were unambiguously identified and distinguished by extensive spectroscopic analyses, NMR calculations with DP4+ analysis, electronic circular dichroism (ECD) calculations and X-ray diffraction analyses. Compounds 1 , 3 , and 4 showed inhibitory activities against the production of inflammatory cytokines (PGE 2 , NO, IL-6 and TNF- α) in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. [Display omitted] • Six previously unreported sesquiterpenoids, Arteannoides U–Z were obtained from the dried aerial parts of Artemisia annua. • Comp. 1~ 4 are four stereoisomers that possess the same planar connectivity, but differ from each other in configuration. • Their structures were identified by extensive spectroscopic analyses, NMR and ECD calculations, X-ray diffraction. • Comp. 1, 3 ~ 4 showed inhibitory activities against the production of PGE 2 , NO, IL-6, TNF-α in LPS induced RAW 264.7. [ABSTRACT FROM AUTHOR]

Seven stilbenes and one catechin were bioactivity-guidedly isolated from the rhizomes of Rheum palmatem . Their structures were identified as piceatannol (1), resveratrol (2), piceid (3), rhapontigenin (4), piceatannol-3 ´ -O-β-D-glucopyranoside (5), rhaponticin (6), catechin (7) and desoxyrhapontigenin (8). Anti-monoamine oxidase (MAO) activities of compounds 1-8 were tested. Compounds 1 and 8 showed significant MAO inhibitory activities with IC 50 values 16.4 ± 1.5 μM and 11.5 ± 1.1, respectively, when the IC 50 value of iproniazid as a standard was 6.5 ± 0.5 μM. The selectivity of compounds 1-8 against MAO-A and MAO-B were also evaluated. The results showed that compounds 4˴6˴8 preferred to inhibit MAO-A rather than MAO-B with selectivity values ([IC 50 of MAO-B]/ [IC 50 of MAO-A]) of 4.74, 10.01 and 9.42, respectively. The preliminary structure-activity relationships (SARs) of these compounds were discussed and the molecular modeling was also performed to explore the binding mode of inhibitors at the active site of MAO-A and MAO-B.