Photo-Controlled Calcium Overload from Endogenous Sources for Tumor Therapy.

Designing reactive calcium-based nanogenerators to produce excess calcium ions (Ca2+ ) in tumor cells is an attractive tumor treatment method. However, nanogenerators that introduce exogenous Ca2+ are either overactive incapable of on-demand release, or excessively inert incapable of an overload of calcium rapidly. Herein, inspired by inherently diverse Ca2+ -regulating channels, a photo-controlled Ca2+ nanomodulator that fully utilizes endogenous Ca2+ from dual sources was designed to achieve Ca2+ overload in tumor cells. Specifically, mesoporous silica nanoparticles were used to co-load bifunctional indocyanine green as a photodynamic/photothermal agent and a thermal-sensitive nitric oxide (NO) donor (BNN-6). Thereafter, they were coated with hyaluronic acid, which served as a tumor cell-targeting unit and a gatekeeper. Under near-infrared light irradiation, the Ca2+ nanomodulator can generate reactive oxygen species that stimulate the transient receptor potential ankyrin subtype 1 channel to realize Ca2+ influx from extracellular environments. Simultaneously, the converted heat can induce BNN-6 decomposition to generate NO, which would open the ryanodine receptor channel in the endoplasmic reticulum and allow stored Ca2+ to leak. Both in vitro and in vivo experiments demonstrated that the combination of photo-controlled Ca2+ influx and release could enable Ca2+ overload in the cytoplasm and efficiently inhibit tumor growth.

Hugan Qingzhi tablets attenuates endoplasmic reticulum stress in nonalcoholic fatty liver disease rats by regulating PERK and ATF6 pathways.

BACKGROUND: Endoplasmic reticulum (ER) stress, promoting lipid metabolism disorders and steatohepatitis, contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablets (HQT) has a definite effect in the clinical treatment of NAFLD patients, but its mechanism is still unclear. This study aims to investigate the effects of HQT on ER stress in the liver tissues of NAFLD rats and explore the underlying mechanism. METHODS: The NAFLD rat model was managed with high-fat diet (HFD) for 12weeks. HQT was administrated in a daily basis to the HFD groups. Biochemical markers, pro-inflammatory cytokines, liver histology were assayed to evaluate HQT effects in HFD-induced NAFLD rats. Furthermore, the expression of ER stress-related signal molecules including glucose regulating protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic translation initiation factor 2α (EIF2α), p-EIF2α, activating transcription factor 4 (ATF4), acetyl-coenzyme A-carboxylase (ACC), activating transcription factor (ATF6), and nuclear factor-kappa B-p65 (NF-κB-p65) were detected by western blot and/or qRT-PCR. RESULTS: The histopathological characteristics and biochemical data indicated that HQT exhibited protective effects on HFD-induced NAFLD rats. Furthermore, it caused significant reduction in the expression of ERS markers, such as GRP78, PERK, p-PERK, and ATF6, and subsequently downregulated the expression of EIF2α, p-EIF2α ATF4, ACC, and NF-κB-p65. CONCLUSIONS: The results suggested that HQT has protective effect against hepatic steatosis and inflammation in NAFLD rats by attenuating ER stress, and the potential mechanism is through inhibition of PERK and ATF6 pathways.

Near-Infrared Conjugated Polymers Containing Thermally Activated Delayed Fluorescence Units Enable Enhanced Photothermal Therapy.

Photothermal therapy (PTT) using near-infrared (NIR) conjugated polymers as photosensitizers has exhibited enormous potential for tumor treatment. However, most NIR conjugated polymers have poor therapeutic efficacy due to their faint absorbance in the NIR region and low photothermal conversion efficiency (PCE). Herein, a valuable strategy for designing NIR polymeric photosensitizer PEKBs with an enhanced PCE accompanied by strong NIR absorbance is proposed by means of inserting TPA-AQ as a thermally activated delayed fluorescence unit into a polymeric backbone. In these PEKBs, PEKB-244 with the appropriate molar content of the TPA-AQ unit displays the strongest NIR absorbance and the highest PCE of 64.5%. Theoretical calculation results demonstrate that the TPA-AQ unit in the polymeric backbone can modulate the intramolecular charge transfer effects and the excited energy decay routes for generating higher heat. The prepared nanoparticles (PEKB-244 NPs) exhibit remarkable photothermal conversion capacities and great biocompatibility in aqueous solutions. Moreover, PEKB-244 NPs also show outstanding photothermal stability, displaying negligible changes in the absorbance within 808 nm irradiation of 1 h (800 mW cm-2). Both in vitro and in vivo experimental results further indicate that PEKB-244 NPs can substantially kill cancer cells under NIR laser irradiation. We anticipate that this novel molecular design strategy can be employed to develop excellent NIR photosensitizers for cancer photothermal therapy.

Chinese herb related molecules Catechins, Caudatin and Cucurbitacin-I inhibit the proliferation of glioblastoma by activating KDELR2-mediated endoplasmic reticulum stress.

Brain gliomas are difficult in the field of tumor therapy because of their high recurrence rate, high mortality rate, and low selectivity of therapeutic agents. The efficacy of Traditional Chinese Medicine (TCM) in the treatment for tumours has been widely recognized. Here, three Chinese herb related molecules, namely Catechins, Caudatin and Cucurbitacin-I, were screened by bioinformatic means, and were found to inhibit the proliferation of glioblastoma T98G cells using Colony-forming and CCK-8 assays. Notably, the simultaneous use of all three molecules could more significantly inhibit the proliferation of glioma cells. Consistent with this, temozolomide, each in the combination with three molecules, could synergistically inhibit the proliferation of T98G cells. Results of qPCR assay was also showed that this inhibition was through the activation of the KDELR2-mediated endoplasmic reticulum stress (ER) pathway. Molecular docking experiments further revealed that Catechins, Caudatin and Cucurbitacin-I could activate ER stress might by targeting KDELR2. Taken together, these results suggest that these herbal molecules have the potential to inhibit the growth of glioma cells and could provide a reference for clinical therapeutic drug selection.

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota.

Nonalcoholic fatty liver disease (NAFLD) has gradually become one of the most serious liver diseases threatening human health in the world. Currently, Chinese herbal medicine is a potentially important treatment option for NAFLD, and the development of effective Chinese herbal medicine has a good prospect. Previous studies have suggested that Ficus hirta Vahl. (FV) has various protective effects on the liver. In this study, we investigated the therapeutic outcomes of FV treatment for the liver disease and its underlying mechanism using HepG2 cell lines induced by palmitate (PA) and mouse model fed with high-fat diet (HFD). FV mainly exerts pharmacological effects by mediating lipid metabolism and inflammation. During the lipid metabolism regulation process, CD36, SREBP-1, SCD1, PPAR γ, ACOX1, and CPT1α are the key factors related to the healing effects of FV on NAFLD. During the inflammation process, the downregulation of IL-6, IL-1ß, and TNF-α is involved in alleviation of NAFLD. Furthermore, CD36 overexpression promotes lipid abnormal metabolism and inflammation in PA-induced HepG2 cells, while CD36 knockdown and FV supplementation reverse these responses. In addition, FV also modulates gut microbiota composition, such as Allobaculum, Faecalibaculum, and Butyricicoccus in HFD-fed mice. In summary, our findings demonstrated that FV exerted a beneficial preventive and therapeutic effect on NAFLD by improving lipid metabolism and inflammation as well as regulating the structure of gut microbiota, and therefore, FV may be a candidate for the treatment of NAFLD.

Estrogen supplementation deteriorates visceral adipose function in aged postmenopausal subjects via Gas5 targeting IGF2BP1.

Increased visceral fat is strongly associated with a series of metabolic complications. Postmenopausal women have an increased risk of visceral fat accumulation, metabolic disorders, and a high incidence of cardiovascular events. However, the effect of estrogen replacement therapy on visceral adipose tissue among postmenopausal women of different ages remains controversial, and the underlying mechanism remains unclear. Hence, it is important to understand when estrogen replacement therapy affects the function of visceral adipose tissue (VAT). Therefore, we collected VAT from pre- and post-menopausal females and we observed increased pro-inflammatory cytokines and insulin resistance-inducing factors, decreased insulin-sensitizing factors, and thermogenic factors in VAT of postmenopausal women. The analysis of adipocytes isolated from the VAT of females of different ages indicated that adiponectin and browning signature genes were significantly decreased with estrogen treatment in postmenopausal women, but were not altered in the young group. Estrogen supplementation in aged female mice (22 m) significantly prevented visceral fat accumulation. However, it deteriorated VAT function by inducing pro-inflammatory cytokines and insulin resistance-inducing factors and decreasing insulin-sensitizing and thermogenic factors. Mechanistically, estrogen induced the expression of long non-coding RNA Gas5 via binding ERα in premenopausal women, which therefore suppressed IGF2BP1 to maintain VAT function. After menopause, with the reversal of ERα/ERß ratio in VAT, estrogen supplementation mainly worked through ERß, which led to low expression levels of Gas5 and eventually caused VAT dysfunction. Our study demonstrated the adverse effects of estrogen supplementation on VAT function in aged postmenopausal population and further elucidated the involved mechanism.

Effective Therapy of Drug-Resistant Bacterial Infection by Killing Planktonic Bacteria and Destructing Biofilms with Cationic Photosensitizer Based on Phosphindole Oxide.

Developing effective therapies to fight against biofilm-associated infection is extremely urgent. The complex environment of biofilm forces the bacteria to evade the elimination of antibiotics, resulting in recalcitrant chronic infections. To address this issue, a cationic antibacterial agent based on phosphindole oxide (ß-PM-PIO) is designed and prepared. The unique molecular structure endows ß-PM-PIO with aggregation-induced emission feature and efficient singlet oxygen generation ability. ß-PM-PIO shows excellent visual diagnostic function to planktonic bacteria and biofilm. In addition, owing to the synergistic effect of phototoxicity and dark toxicity, ß-PM-PIO can achieve superb antibacterial and antibiofilm performance against Gram-positive bacteria with less potential of developing drug resistance. Notably, ß-PM-PIO also holds excellent anti-infection capacity against drug-resistant bacteria in vivo with negligible side effects. This work offers a promising platform to develop advanced antibacterial agents against multidrug-resistant bacterial infection.

Traditional Chinese medicine suppressed cancer progression by targeting endoplasmic reticulum stress responses: A review.

Cancer has a high morbidity and mortality; therefore, it poses a major global health concern. Imbalance in endoplasmic reticulum homeostasis can induce endoplasmic reticulum stress (ERS). ERS has been shown to play both tumor-promoting and tumor-suppressive roles in various cancer types by activating a series of adaptive responses to promote tumor cell survival and inducing ERS-related apoptotic pathways to promote tumor cell death, inhibit tumor growth and suppress tumor invasion. Because multiple roles of ERS in tumors continue to be reported, many studies have attempted to target ERS in cancer therapy. The therapeutic effects of traditional Chinese medicine (TCM) treatments on tumors have been widely recognized. TCM treatments can enhance the sensitivity of tumor radiotherapy, delay tumor recurrence and improve patients' quality of life. However, there are relatively few reports exploring the antitumor effects of TCM from the perspective of ERS. This review addresses the progress of TCM intervention in tumors via ERS with a view to providing a new direction for tumor treatment.

The probiotic effects of AB23A on high-fat-diet-induced non-alcoholic fatty liver disease in mice may be associated with suppressing the serum levels of lipopolysaccharides and branched-chain amino acids.

Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from Rhizoma alisamatis that has been widely used as a traditional Chinese medicine (TCM). Previous studies have documented the beneficial effect of AB23A on non-alcoholic fatty liver disease (NAFLD), but the functional interactions between gut microbiota and the anti-NAFLD effect of AB23A remain unclear. In this study, we investigated the benefits of experimental treatment with AB23A on gut microbiota dysbiosis in NAFLD with an obesity model. C57BL/6J mice were administrated a high-fat diet (HFD) with or without AB23A for 12 weeks. AB23A significantly improved metabolic phenotype in the HFD-fed mice. Moreover, results of 16S rRNA gene-based amplicon sequencing in each group reveled that AB23A not only reduced the abundance of the Firmicutes/Bacteroidaeota ratio and Actinobacteriota/Bacteroidaeota ratio, but regulated the abundance of the top 10 genera, including norank_f__Muribaculaceae, Lactobacillus, Ileibacterium, Turicibacter, Faecalibaculum, the Lachnospiraceae_NK4A136_group, unclassified_f__Lachnospiraceae, and norank_f__Lachnospiraceae. AB23A significantly reduced the serum levels of lipopolysaccharide and branched-chain amino acids, which are positively correlated with the abundances of Ileibacterium and Turicibacter. Moreover, AB23A led to remarkable reductions in the activation of TLR4, NF-κB, and mTOR, and upregulated the expression of tight junction proteins, including ZO-1 and occludin. These results revealed that AB23A displayed a prebiotic capacity in HFD-fed NAFLD mice.

9,10-Phenanthrenequinone: A Promising Kernel to Develop Multifunctional Antitumor Systems for Efficient Type I Photodynamic and Photothermal Synergistic Therapy.

Synergistic phototherapy provides a promising strategy to conquer the hypoxia and heterogeneity of tumors and realize a better therapeutic effect than monomodal photodynamic therapy (PDT) or photothermal therapy (PTT). The development of efficient multifunctional organic phototheranostic systems still remains a challenging task. Herein, 9,10-phenanthrenequinone (PQ) with strong electron-withdrawing ability is conjugated with the rotor-type electron-donating triphenylamine derivatives to create a series of tailor-made photosensitizers. The highly efficient Type I reactive oxygen species generation and outstanding photothermal conversion capacity are tactfully integrated into these PQ-cored photosensitizers. The underlying photophysical and photochemical mechanisms of the combined photothermal and Type I photodynamic effects are deciphered by experimental and theoretical methods and are closely associated with the active intramolecular bond stretching vibration, facilitated intersystem crossing, and specific redox cycling activity of the PQ core. Both in vitro and in vivo evaluations demonstrate that the nanoagents fabricated by these PQ-based photosensitizers are excellent candidates for Type I photodynamic and photothermal combined antitumor therapy. This study thus broadens the horizon for the development of high-performance PTT/Type I PDT nanoagents for synergistic phototheranostic treatments.

Improving Image-Guided Surgical and Immunological Tumor Treatment Efficacy by Photothermal and Photodynamic Therapies Based on a Multifunctional NIR AIEgen.

Multimodal therapy is attracting increasing attention to improve tumor treatment efficacy, but generally requires various complicated ingredients combined within one theranostic system to achieve multiple functions. Herein, a multifunctional theranostic nanoplatform based on a single aggregation-induced-emission luminogen (AIEgen), DDTB, is designed to integrate near-infrared (NIR) fluorescence, photothermal, photodynamic, and immunological effects. Intravenously injected AIEgen-based nanoparticles can efficiently accumulate in tumors with NIR fluorescence to provide preoperative diagnosis. Most of the tumors are excised under intraoperative fluorescence navigation, whereafter, some microscopic residual tumors are completely ablated by photodynamic and photothermal therapies for maximally killing the tumor cells and tissues. Up to 90% of the survival rate can be achieved by this synergistic image-guided surgery and photodynamic and photothermal therapies. Importantly, the nanoparticles-mediated photothermal/photodynamic therapy plus programmed death-ligand 1 antibody significantly induce tumor elimination by enhancing the effect of immunotherapy. This theranostic strategy on the basis of a single AIEgen significantly improves the survival of cancer mice with maximized therapeutic outcomes, and holds great promise for clinical cancer treatment.

Research progress on culture technologies,chemical components,and pharmacological activities of Saussurea involucrata cells / 中国中药杂志

Saussurea involucrata,a traditional Chinese medicinal material,is effective in the treatment of rheumatoid arthritis with cold-dampness blockage syndrome,cold pain in lower abdomen,and menstrual irregularities. However,due to the specific habitat,low natural reproduction rate,slow growth,and overexploitation,it is at the high risk of extinction. S. involucrata cells can be obtained through callus culture,suspension culture,and hairy root culture. This study highlighted the influences of reactor type,culture system,precursor,elicitor type, and light wavelength on the suspension culture of S. involucrate cells. The chemical components of S. involucrata cells mainly include phenylpropanoids,flavonoids,lignans,and steroids,among which phenylpropanoids are the most abundant. S. involucrata cells have multiple pharmacological activities of anti-inflammation,analgesia,activating blood and resolving stasis,immunoregulation,increasing bone density,lowering blood lipids,anti-hypoxia,anti-exercise fatigue,anti-radiation,anti-obesity,and anti-oxidation. Moreover,it has the potential of treating aplastic anemia. This study reviews the cell culture technologies,chemical components,and pharmacological activities of S. involucrata cells,laying a basis for the further research,development,and utilization.

Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19~+B cells regulating FAK/CAPN/PI3K pathway / 中国中药杂志

To observe the effect of Xinfeng Capsules on rheumatoid arthritis (RA) B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin (HGB),platelet count (PLT),erythrocyte sedimentation (ESR),immunoglobulin (Ig) G,Ig A,Ig M,rheumatoid factor (RF),anti-cyclic citrulline antibody (CCP-AB),C-reactive protein (CRP)]were detected.ELISA was used to detect serum interleukin (IL)-1β，IL-10,IL-33,chemokine 5 (CCL5),and vascular endothelial growth factor (VEGF).CD3~-CD19~+B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β，IL-33,CCL5,VEGF,CD3~-CD19~+B cells,FAK,p-FAK,CAPN,PI3K expressions (P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3~-CD19~+,regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.

Hugan Qingzhi medication ameliorates free fatty acid-induced L02 hepatocyte endoplasmic reticulum stress by regulating the activation of PKC-δ.

BACKGROUND: Previous studies have found that Hugan Qingzhi tablet (HQT) has significant lipid-lowering and antioxidant effects on non-alcoholic fatty liver disease (NAFLD). Moreover, the results of proteomic analysis confirmed that various proteins in endoplasmic reticulum stress (ERS) pathway were activated and recovered by HQT. However, its mechanism remains confused. The purpose of this study was to explore the effects of HQT-medicated serum on hepatic ERS and its relevant mechanisms. METHODS: L02 cells were induced by Free Fatty Acid (FFA) for 24 h to establish a model of hepatic ERS and pretreated with the drug-medicated rat serum for 24 h. Accumulation of intracellular lipid was evaluated using Oil Red O staining and Triglyceride detection kit. The morphological changes of ER were observed by TEM. PKC-δ was silenced by specific siRNA. Western blot and RT-qPCR were applied to detect the expression of markers related to ERS, calcium disorder, steatosis and insulin resistance. The fluorescence of Ca2+ influx was recorded using fluorescence spectrophotometer. RESULTS: HQT-medicated serum significantly decreased the intracellular TG content. Furthermore, it caused significant reduction in the expression of ERS markers and an improvement in ER structure of L02 cells. PKC-δ was activated into phosphorylated PKC-δ in FFA-induced L02 hepatocytes while these changes can be reversed by HQT-medicated serum. Silencing PKC-δ in L02 cells can restore the expression and activity of SERCA2 in ER and down-regulate the expression of IP3R protein to maintain intracellular calcium homeostasis, so as to relieve FFA-induced ERS and its lipid accumulation and insulin resistance. CONCLUSIONS: The results concluded that HQT-medicated serum exerts protective effects against hepatic ERS, steatosis and insulin resistance in FFA-induced L02 hepatocyte. And its potential mechanism might be down-regulating the activation of PKC-δ and stabilization of intracellular calcium.

Nanococktail Based on AIEgens and Semiconducting Polymers: A Single Laser Excited Image-Guided Dual Photothermal Therapy.

Semiconducting polymers (SPs)-based dual photothermal therapy (PTT) obtained better therapeutic effect than single PTT due to its higher photothermal conversion efficiency. However, most dual PTT need to use two lasers for heat generation, which brings about inconvenience and limitation to the experimental operations. Herein, we report the development of "nanococktail" nanomaterials (DTPR) with 808 nm-activated image-guided dual photothermal properties for optimized cancer therapy. Methods: In this work, we co-encapsulated AIEgens (TPA-BDTO, T) and SPs (PDPPP, P) by using maleimide terminated amphiphilic polymer (DSPE-PEG2000-Mal, D), then further conjugated the targeting ligands (RGD, R) through "click" reaction. Finally, such dual PTT nanococktail (termed as DTPR) was constructed. Results: Once DTPR upon irradiation with 808 nm laser, near-infrared fluorescence from T could be partially converted into thermal energy through fluorescence resonance energy transfer (FRET) between T and P, coupling with the original heat energy generated by the photothermal agent P itself, thus resulting in image-guided dual PTT. The photothermal conversion efficiency of DTPR reached 60.3% (dual PTT), much higher as compared to its inherent photothermal effect of only 31.5% (single PTT), which was further proved by the more severe photothermal ablation in vitro and in vivo upon 808 nm laser irradiation. Conclusion: Such smart "nanococktail" nanomaterials could be recognized as a promising photothermal nanotheranostics for image-guided cancer treatment.

Vasorelaxant 4,5-seco-abietane diterpenoids with diverse 6/6/6, 6/6/7, and 6/6/8 architectures from Salvia prattii Hemsl.

Salpratins A-D (1-4), four new 4,5-seco-abietane diterpenoids, along with twelve known analogues, featuring diverse 6/6/6, 6/6/7, and 6/6/8 rings system, were isolated from Salvia prattii Hemsl. Particularly, salpratin A is the first example of 4,5;12,13-bis-seco-abietane diterpenoid features with a 5/6/6/6 ring system. Their structures were determined by analyses of comprehensive NMR and MS spectroscopic data and single-crystal X-ray diffractions. In addition, compounds 1, 3, 4, 6, 7, 8 and 14 showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.

Carbon dots as an "on-off-on" fluorescent probe for detection of Cu(II) ion, ascorbic acid, and acid phosphatase.

Carbon dot (CD)-based fluorescent probes have been widely exploited; however, multi-component detection using CDs without tedious surface modification is always a challenging task. Here, we develop a convenient and simple CD-based "on-off-on" fluorescent probe for detection of copper(II) ion (Cu2+), ascorbic acid (AA), and acid phosphatase (ACP). Cu2+ leads to the fluorescence quenching of CDs. The limit of detection (LOD) for Cu2+ is 2.4 µM. When AA is added into the CDs + Cu2+ solution, Cu2+ is reduced by AA to Cu+, causing the fluorescence recovery of CDs. The fluorescent intensity linearly correlates with the concentration of AA in the range of 100-2800 µM with LOD of 60 µM. Besides, the probe has potential application for detection of AA in real samples such as VC tablets, orange juice, and fresh orange. The probe can also indirectly detect ACP that enzymatically hydrolyzes ascorbic acid-phosphate (AAP) to produce AA. This work expands the application of CDs in the multi-component detection and provides a facile fluorescent probe for detection of AA in real samples. Graphical abstract.

New 4,5-seco-20(10→5)-abeo-Abietane Diterpenoids with Anti-Inflammatory Activity from Isodon lophanthoides var. graciliflorus (Benth.) H.Hara.

Three new 4,5-seco-20(10→5)-abeo-abietane diterpenoids, 16-hydroxysalvilenone (1), 15-hydroxysalprionin (2), and 11ß,15-dihydroxysalprionin-12-one (3), and nine known abietane diterpenoids, 4-12, along with one known sempervirane diterpenoid, hispidanol A (13), were isolated from the aerial parts of Isodon lophanthoides var. graciliflorus. The structures of compounds 1-3 were determined on the basis of spectroscopic methods including extensive analysis of NMR and mass spectroscopic data. All diterpenoids were tested for their TNF-α inhibitory effects on LPS-induced RAW264.7 cells. Compound 9 (16-acetoxyhorminone) was the most potent with an IC50 value of 3.97±0.70 µm.

Prenylated Acylphloroglucinols from Hypericum faberi.

The isolation and structure elucidation of six new prenylated acylphloroglucinols, faberiones A-F, from the whole plant of Hypericum faberi is reported. Faberiones A-D (1-4) share a rare styrene substituent and may be biosynthetically generated via further acylation of the acylphloroglucinols. By analyzing the MS and NMR data, the structures of the new isolates were established. Faberiones B (2) and C (3) showed moderate cytotoxicity against the pancreatic cell line (PANC-1) with IC50 values of 6.2 and 9.0 µM, respectively.