Discovery of sesquiterpene from Youngia japonica with antitumor effect.

Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.

The effect of COVID-19 infection on patients with rheumatic diseases in China.

OBJECTIVES: At the end of 2022, the COVID-19 outbreak erupted in China, and BA.5.2 or BF.7 subtypes of Omicron novel variations were implicated in more than 90% of the cases. We created a real-world questionnaire survey to better understand how this new variant pandemic was affecting rheumatic patients in China. METHODS: During the COVID-19 outbreak in China, the subjects of this study were rheumatic patients and non-rheumatic individuals (control group), who were matched for sex and age. Professional physicians carefully questioned the participants before administering a questionnaire as part of the study. This study focused on the general baseline characteristics, clinical symptoms and treatment after COVID-19 infection, and the target populations' awareness of COVID-19. RESULTS: The study included 1130 participants, of whom 572 were assigned to the rheumatic group and 558 to the control group. The percentage of vaccinated controls was significantly higher than that of rheumatic patients (90.1% vs. 62.8%, p < 0.001), while the rate of COVID-19 infection was not significantly different between the two groups (82.3% vs. 86.6%, p = 0.051). Patients with rheumatic disease experienced substantially more days of fever following infection (2.87 ± 3.42 vs. 2.18 ± 1.65, p = 0.002) compared to individuals in the control group. The rheumatic patients had a greater prevalence of cough (67.1% vs. 54.0%, p < 0.001), somnipathy (13.8% vs. 6.0%, p < 0.001), and conjunctivitis/ophthalmodynia (5.3% vs. 2.1%, p = 0.008), while dry throat/throat pain/weakness (49.9% vs. 59.4%, p = 0.003), myalgia/osteodynia (33.3% vs. 41.8%, p = 0.003), and dyspnea (14.0% vs. 25.3%, p < 0.001) were more likely to occur in non-rheumatic group after infection. Human immunoglobulin (2.1% vs. 0.2%, p = 0.006), glucocorticoids (19.5% vs. 1.6%, p < 0.001), oxygen support (6.8% vs. 2.1%, p < 0.001), and traditional Chinese medicine (21.9% vs. 16.6%, p = 0.037) were all more frequently used by rheumatic patients with COVID-19 infection. People in the control group were more confused about whether to use masks in following social activities after contracting COVID-19 (14.7% vs. 7.6%, p = 0.001). In the control group, more individuals than patients with rheumatic disease (25.1% vs. 13.4%, p < 0.001) expressed an interest to receive the vaccine again. After being exposed to COVID-19, the majority of rheumatic patients (66.9%) reported no discernible change, only 29.1% reported a worsening of their symptoms, and the remaining 4% indicated an improvement. CONCLUSIONS: After the COVID-19 outbreak in China, the proportion of patients with rheumatic diseases infected with the virus was similar to that of normal individuals. But the clinical symptoms, follow-up treatment requirements, and awareness of the COVID-19 among rheumatic patients were distinct from those among non-rheumatic patients, necessitating the use of individualized diagnosis and treatment plans as well as health advice by medical professionals in clinical work. Key Points • Despite there were different comorbidities and vaccination rates, the rate of COVID-19 infection in patients with rheumatic disease was similar to that of normal individuals. • After COVID-19 infection, rheumatic patients and normal controls had different clinical symptoms and drug usage. • After being exposed to COVID-19, the majority of rheumatic patients felt no significant change in the primary disease, while the normal controls was more likely to accept a new vaccine injection and confused about whether to use masks in following social activities.

Anti-osteoporotic drugs affect the pathogenesis of gut microbiota and its metabolites: a clinical study.

Background: Disordered gut microbiota (GM) structure and function may contribute to osteoporosis (OP). This study explores how traditional Chinese medicine (TCM) intervention affects the structure and function of the GM in patients with OP. Method: In a 3-month clinical study, 43 patients were randomly divided into two groups receiving conventional treatment and combined TCM (Yigu decoction, YGD) treatment. The correlation between the intestinal flora and its metabolites was analyzed using 16S rDNA and untargeted metabolomics and the combination of the two. Results: After three months of treatment, patients in the treatment group had better bone mineral density (BMD) than those in the control group (P < 0.05). Patients in the treatment group had obvious abundance changes in GM microbes, such as Bacteroides, Escherichia-Shigella, Faecalibacterium, Megamonas, Blautia, Klebsiella, Romboutsia, Akkermansia, and Prevotella_9. The functional changes observed in the GM mainly involved changes in metabolic function, genetic information processing and cellular processes. The metabolites for which major changes were observed were capsazepine, Phe-Tyr, dichlorprop, D-pyroglutamic acid and tamsulosin. These metabolites may act through metabolic pathways, the citrate cycle (TCA cycle) and beta alanine metabolism. Combined analysis showed that the main acting metabolites were dichlorprop, capsazepine, D-pyroglutamic acid and tamsulosin. Conclusion: This study showed that TCM influenced the structure and function of the GM in patients with OP, which may be one mechanism by which TCM promotes the rehabilitation of patients with OP through the GM.

Comparing the effectiveness of type of the traditional Chinese exercises, frequency, intensity, time in osteoporosis: a protocol for systematic evaluation and network meta-analysis of randomised controlled trials.

INTRODUCTION: As populations age, osteoporosis has become a hot topic of global public concern. The beneficial effects of traditional Chinese exercises on the musculoskeletal system have been demonstrated. However, previous research findings on osteoporosis are inconsistent, and it is unclear which type of exercise and its frequency and duration have the best effect on osteoporosis. This study aims to investigate the most appropriate exercise modality for people with osteoporosis through systematic evaluation and network meta-analysis to guide clinical practice. METHODS AND ANALYSIS: The Cochrane Library, Web of Science, MEDLINE, Embase, China Biomedical Literature, China Knowledge Network, China Science and Technology Journal and Wanfang databases will be searched until January 2022. The language of the articles should be English or Chinese. All clinical randomised controlled trials on the effect of traditional Chinese exercises on osteoporosis will be included. We will use RevMan, Stata and GeMTC software to complete our network meta-analysis. We will perform risk of bias assessment, subgroup analysis and sensitivity analysis to correct the results. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluation guideline development tool and Confidence in Network Meta-Analysis (CINeMA, a new method for assessing CINeMA results) approach to evaluate the reliability of our final results. ETHICS AND DISSEMINATION: All data for this study will be obtained from published studies, so no ethical review will be needed. We will publish the results of the study in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022323622.

Advances of targeting the YAP/TAZ-TEAD complex in the hippo pathway for the treatment of cancers.

The Hippo pathway is an evolutionarily conserved signaling pathway that plays critical roles in the tumorigenesis and progression of breast cancer, oral cancer, rectal cancer, colloid cancer, and so on. YAP/TAZ-TEAD complex is a key knot in the Hippo pathway regulating cell proliferation and stem cell functions. Activation or overexpression of this complex has been proved to lead to cell transformation, proliferation and eventually cancerization. In this review, the association between the alterations of hippo pathway and tumorigenesis of various cancer had been elucidated. The structural basis of YAP/TAZ-TEAD complex is analyzed, and the targeting inhibitors are summarized within the medicinal chemistry classification. Moreover, we have also discussed the clinical status and current challenges of these drug candidates, and provide guidance for the future development of inhibitors targeting this pathway, especially YAP/TAZ-TEAD complex.

Polyhydric Stigmastane-Type Steroids Derivative from Vernonia amygdalina and Their Anti-Neuroinflammatory Activity.

Vernonia amygdalina Del. is a traditional medicinal plant and vegetable originating from tropical Africa. The phytochemical investigation of V. amygdalina led to eight undescribed polyhydric stigmastane-type steroids, vernonin M-T (1-8). Their gross structures and stereochemistry were elucidated by HR-ESI-MS, 1D and 2D NMR spectra, X-ray diffraction, quantum chemical computation of the ECD spectrum, and the in situ dimolybdenum CD method. The anti-neuroinflammatory activity of the isolated compounds was performed in BV-2 microglia cells. As a result, compound 1 displayed a notable anti-neuroinflammatory effect via suppressing the LPS-induced IκB degradation and restricting the activation of the PI3K/AKT and p38 MAPK pathways.

Tautomeric phytosterols from Vernonia amygdalina Delile and their anti-cervical cancer activity.

Vernonia amygdalina Delile is generally used as green vegetables for cuisine in Nigeria and health tea or products in southeast of china. It was also used as folk medicine for the treatment of anti-helminth, febrifuge, digestive tonic and wounds. In this study, eleven undescribed phytosterols (1-2, 4-12) and six known analogues (3, 13-17) were isolated from the stems of V. amygdalina. Their structures including absolute configurations were elucidated by comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS), X-ray diffraction and comparison of their ECD spectra. Besides, the tautomerism of phytosterols (1, 3-6, 12-17) with hemiacetal moiety were analyzed by solution NMR with different deuterated solvent and variable-temperature experiments. In addition, the cytotoxic activities of isolates against HeLa cells were evaluated. As a result, compound 10 exhibited the most potent anti-cervical cancer activity with the IC50 of 22.44 µM. Mechanism studies indicated that 10 triggered HeLa cells apoptosis through activating caspase signaling pathway. Furthermore, 10 could arrest the cell cycle in S phase and suppress the activation of the PI3K/AKT/mTOR pathway, leading to the inhibition of HeLa cells proliferation.

Seco-polyprenylated acylphloroglucinols from Hypericum elodeoides induced cell cycle arrest and apoptosis in MCF-7 cells via oxidative DNA damage.

Four undescribed seco-polyprenylated acylphloroglucinols (seco-PAPs), elodeoidesones A-D (1-4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6-seco-PAPs with fascinating 5/5 fused ring, while 2-4 possess a 1,2-seco-PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1-4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC50 value of 7.34 µM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage.

[Lignans from Agrimonia pilosa].

Thirteen lignans were isolated from 60% ethanol extract of Agrimonia pilosa by column chromatography over silica gel, ODS, and MCI and preparative high performance liquid chromatography(HPLC). Their chemical structures were identified by physiochemical properties and spectral data as(7S,8S)-threo-4,7,9,9'-tetrahydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan(1),(+)-4,9,9'-trihydroxy-3-methoxy-3',7-epoxy-8,4'-oxyneolignan(2), dihydrodehydro-diconiferyl alcohol(3), 4,9,9'-trihydroxy-3,3',5-trimethoxy-4',7-epoxy-8,5'-neolignan(4),(-)-secoisolariciresinol(5), 4,7,9,9'-tetrahydroxy-3,3',5'-trimethoxy-8-O-4'-neolignan(6),(+)-isolariciresinol(7), 4,7,9,9'-tetrahydroxy-3,3'-dimethoxy-8-O-4'-neolignan(8), burselignan(9),(-)-evofolin B(10), icariol A2(11), ciwujiatone(12), and(+)-4″,4-dihydroxy-3,3',3″,3,5,5'-hexamethoxy-7,9';7',9-diepoxy-4,8″;4',8-bisoxy-8,8'-dineolignan-7″,7,9″,9-tetraol(13). Compound 1 was a new compound, and compounds 1-13 were isolated from Agrimonia plant for the first time. This study can enrich the chemical components in A. pilosa and provide material conditions for the follow-up study of its biological activity and the elucidation of its pharmacodynamic substances.

Dysideanones F-G and dysiherbols D-E, unusual sesquiterpene quinones with rearranged skeletons from the marine sponge Dysidea avara.

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC50 values of 10.2 and 8.6 µmol·L-1, respectively.

Inhibitory effects of phenolic glycosides from Trollius chinensis Bunge on α-glucosidase: inhibition kinetics and mechanisms.

Two undescribed phenolic glycosides, trochinenols B and C (1 and2), together with four known analogues (3-6), were isolated from the functional tea Trollius chinensis Bunge and their α-glucosidase inhibitory kinetics and mechanisms were investigated. It was found that 1 inhibited α-glucosidase in a noncompetitive manner with an IC50 value of 25.96 µM, while 3 showed a notable inhibitory effect against α-glucosidase in an uncompetitive manner with an IC50 value of 3.14 µM. Analysis of synchronous fluorescence and circular dichroism spectroscopy indicated that the binding of 1 to α-glucosidase led to the rearrangement and conformational alteration of the α-glucosidase enzyme. Furthermore, molecular docking indicated that 1 had a high affinity close to the active site pocket of α-glucosidase and indirectly inhibited the catalytic activity of the enzyme. However, 3 was bound to the entrance part of the active center of α-glucosidase and could hinder the release of the substrate as well as the catalytic reaction product, eventually suppressing the catalytic activity of α-glucosidase.

A natural product targets BRD4 to inhibit phase separation and gene transcription.

The BET-bromodomain protein BRD4 uses two bromodomains to target acetyl-histones and other domains to recruit P-TEFb and other transcription factors to stimulate transcription of proto-oncogenes and key cell identity genes. Recent studies show that its ability to form phase-separated condensates that cluster preferentially at the super-enhancer regions of target genes is key for BRD4 to exert its functions. Here, we describe the identification of a natural product called PCG from polygonum cuspidatum Sieb.et Zucc., a traditional Chinese medicinal herb, that directly binds to BRD4. This binding inhibits BRD4 phase separation, turns dynamic BRD4 nuclear condensates into static aggregates, and effectively shuts down transcription of BRD4-dependent genes. Thus, through PCG we have discovered a BET inhibitor that not only selectively targets BRD4 but also works by suppressing phase separation, a mechanism of action that is different from those of the other known BET inhibitors.

Cognitive Improvement via Left Angular Gyrus-Navigated Repetitive Transcranial Magnetic Stimulation Inducing the Neuroplasticity of Thalamic System in Amnesic Mild Cognitive Impairment Patients.

BACKGROUND: Stimulating superficial brain regions highly associated with the hippocampus by repetitive transcranial magnetic stimulation (rTMS) may improve memory of Alzheimer's disease (AD) spectrum patients. OBJECTIVE: We recruited 16 amnesic mild cognitive impairment (aMCI) and 6 AD patients in the study. All the patients were stimulated to the left angular gyrus, which was confirmed a strong link to the hippocampus through neuroimaging studies, by the neuro-navigated rTMS for four weeks. METHODS: Automated fiber quantification using diffusion tensor imaging metrics and graph theory analysis on functional network were employed to detect the neuroplasticity of brain networks. RESULTS: After neuro-navigated rTMS intervention, the episodic memory of aMCI patients and Montreal Cognitive Assessment score of two groups were significantly improved. Increased FA values of right anterior thalamic radiation among aMCI patients, while decreased functional network properties of thalamus subregions were observed, whereas similar changes not found in AD patients. It is worth noting that the improvement of cognition was associated with the neuroplasticity of thalamic system. CONCLUSION: We speculated that the rTMS intervention targeting left angular gyrus may be served as a strategy to improve cognitive impairment at the early stage of AD patients, supporting by the neuroplasticity of thalamic system.

A new phenolic glycoside from Trollius chinensis Bunge with anti-inflammatory and antibacterial activities.

A undescribed phenolic glycoside, trochinenol A (1), was isolated from the flowers of Trollius chinensis Bunge and the structure was identified by spectroscopic methods. Its anti-inflammatory and antibacterial effects were investigated by broth microdilution and NF-κB reporter gene assays. Consequently, compound 1 exhibited an appreciable effect against Staphylococcus aureus with the MIC value of 6.25 µg/mL. Besides, it showed moderate effect against TNFα-induced activation of NF-κB pathway.

[Therapeutic mechanism of Psammosilene tunicoides extract on rheumatoid arthritis based on NLRP3 inflammasome].

In this study, we investigated the mechanism of crude extract of Psammosilene tunicoides(CEPT) in the treatment of rheumatoid arthritis(RA) based on the Nod-like receptor protein 3(NLRP3) inflammasome. The collagen-induced arthritis(CIA) mouse model was established. On day 32 after the primary immunization, according to the arthritis score, the mice were randomly divided into model group, positive control(methotrexate) group, low-and high-dose CEPT groups, and normal group, with 10 mice in each group. According to the administration dose of each group, the mice were continuously administered for 21 days. Every four days during the administration, the paw edema degree, arthritis score, and spleen index of the mice were measured; histopathological examination was performed for the ankles of the mice; the contents of IL-1ß and IL-18 in the serum were determined; the protein expression levels of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a CARD(ASC), as well as the mRNA expression levels of NLRP3 and caspase-1 in the ankle joints of the mice were detected. The results showed that compared with those in the model group, the mice in the positive control group and CEPT groups had significantly decreased the contents of IL-1ß and IL-18 in the serum and spleen index(P<0.01), significantly lowered arthritis score and degree of paw edema(P<0.01), alleviated arthritic infiltration of the knee, and down-regulated protein and mRNA levels of NLRP3, ASC, and caspase-1 in the ankle joint(P<0.01). These results suggest that P. tunicoides may reduce the paw edema and arthritis score and alleviate the inflammatory response in CIA mice by inhibiting the expression of NLRP3. This study provides a basis for the study of immune regulation of P. tunicoides in RA.

Quercetin Protects H9c2 Cardiomyocytes against Oxygen-Glucose Deprivation/Reoxygenation-Induced Oxidative Stress and Mitochondrial Apoptosis by Regulating the ERK1/2/DRP1 Signaling Pathway.

Reperfusion of blood flow during ischemic myocardium resuscitation induces ischemia/reperfusion (I/R) injury. Oxidative stress has been identified as a major cause in this process. Quercetin (QCT) is a member of the flavonoid family that exerts antioxidant effects. The aim of this study was to investigate the preventive effects of QCT on I/R injury and its underlying mechanism. To this end, H9c2 cardiomyocytes were treated with different concentrations of QCT (10, 20, and 40 µM) and subsequently subjected to oxygen-glucose deprivation/reperfusion (OGD/R) administration. The results indicated that OGD/R-induced oxidative stress, apoptosis, and mitochondrial dysfunction in H9c2 cardiomyocytes were aggravated following 40 µM QCT treatment and alleviated following the administration of 10 and 20 µM QCT prior to OGD/R treatment. In addition, OGD/R treatment inactivated ERK1/2 signaling activation. The effect was mitigated using 10 and 20 µM QCT prior to OGD/R treatment. In conclusion, these results suggested that low concentrations of QCT might alleviate I/R injury by suppressing oxidative stress and improving mitochondrial function through the regulation of ERK1/2-DRP1 signaling, providing a potential candidate for I/R injury prevention.

Mulberry leaf polysaccharide supplementation contributes to enhancing the respiratory mucosal barrier immune response in Newcastle disease virus-vaccinated chicks.

Despite high global vaccination coverage, Newcastle disease (ND) remains a constant threat to poultry producers owing to low antibody levels. Given the respiratory mucosa is the important site for Newcastle disease virus (NDV) vaccination, enhancing respiratory mucosal immunity may help control ND. Our previous study showed that mulberry leaf polysaccharide (MLP) is very promising in delivering a robust balanced immune response, but the effects of it on respiratory immunity in chicks are unknown. In this study, we evaluated the potential of MLP to activate respiratory mucosal immunity and revealed the possible mechanism of MLP as an immunopotentiator for ND vaccines. Chicks were randomly divided into 5 groups: blank control, vaccination control (VC), and low-, middle-, and high-dose MLP (MLP-L, MLP-M, and MLP-H) (n = 30). The serum results of humoral and cell-mediated immune responses showed significant increases in NDV hemagglutination inhibition antibody titer, IgG and IgA antibody levels, and the T-lymphocyte population in the MLP-M group compared with the VC group. Validation of results also indicated remarkable increases in tracheal antibody-mediated immunity and a mucosal immune response in the MLP-M group. Furthermore, the upregulation of TLR7 revealed a possible mechanism. Our findings provided evidence to consider MLP as a potential mucosal vaccine adjuvant candidate against ND in chickens.

Phenolic glycosides and flavonoids with antioxidant and anticancer activities from Desmodium caudatum.

Descaudatine A (1), an undescribed phenolic glycoside, along with a known analogue (2) and ten flavonoids (3-12), were isolated from the whole plant of Desmodium caudatum. Compounds 1 and 4 exhibited potent antioxidant activities with the IC50 of 58.59 µM and 31.31 µM, respectively, which were approached to that of the positive control Vitamin C (IC50 = 46.32 µM). Meanwhile, 12 showed moderate antioxidant activity with the IC50 of 173.9 µM. Besides, compounds 3 and 6 inhibited the proliferation of HeLa cells with IC50 values of 56.14 µM and 69.04 µM, respectively. Further studies indicated that 3 and 6 could dose-dependently induce PARP cleavage and might trigger caspase-3, 8, 9 activation to induce apoptosis. RXRα is an ideal anticancer target of nuclear receptor. The reporter gene assay of RXRα indicated that 3 and 6 could inhibited the 9-cis-RA induced RXRα transcription in a concentration-dependent manner.

A qualitative classification signature for post-surgery 5-fluorouracil-based adjuvant chemoradiotherapy in gastric cancer.

BACKGROUND AND PURPOSE: Currently, 5-fluorouracil (5-FU)-based adjuvant chemoradiotherapy (ACRT) is a preferred regimen for post-surgery gastric cancer (GC). However, the survival outcome of 5-FU-based ACRT varies greatly among different GC patients. Thus, it is necessary to classify which patients may benefit from 5-FU-based ACRT. MATERIALS AND METHODS: We collected 577 GC and 84 adjacent normal samples for training and 675 GC samples for validation. Based on the within-sample relative expression orderings (REOs) of gene expression levels, reversal gene pairs were selected, and the pairs correlating with overall survival (OS) of GC patients receiving 5-FU-based ACRT were identified as candidates. Finally, an optimized set of candidate gene pairs was selected as a classification signature in training data and validated in validation data. RESULTS: A signature consisting of 34 gene pairs was identified in training data and validated in three independent datasets. The classified low-risk group had better OS than the classified high-risk group. We also analyzed the recurrent free survival or disease free survival (RFS/DFS) of the validation datasets, and the similar results were shown. Furthermore, although the signature was identified based on the OS of GC patients receiving ACRT, it was not a prognostic signature for patients treated with surgery alone, but may be a potential signature for 5-FU-based chemotherapy alone. CONCLUSIONS: The signature can accurately classify GC patients who may benefit from 5-FU-based ACRT, which could aid clinicians in tailoring more effective GC treatments.

Cytotoxic polyprenylated phloroglucinol derivatives from Hypericum elodeoides Choisy modulating the transactivation of RXRα.

Hyperelodione D (1), an undescribed polyprenylated phloroglucinol derivative possessing 6/6/5/5 fused tetracyclic core, together with hyperelodiones E-F (2-3), two unreported analogues bearing 6/5/5 fused tricyclic structure, were isolated from Hypericum elodeoides Choisy. Their planar structures were elucidated by spectroscopic analysis (HRESIMS, 1D and 2D NMR) and their absolute configurations were determined by comparison of experimental and calculated ECD data. The cytotoxicity and retinoid X receptor-α (RXRα) related activities of the isolates were evaluated and the plausible biogenetic pathways of 1-3 were proposed.