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A new phenylpropanoid glycoside, named 4-O-β-D-glucopyranosyl-7-phenyl-9-propenyl ketone-9-O-β-Dglucopyranosyl-(6′′→1′′′)-6′′-O-α-L-rhamnopyranose (1), and four known phenylpropanoid glycosides 2–5 were isolated from highland barley Monascus purpureus Went for the first time. Their structures were determined by their comprehensive spectral data and reported references. Compounds 1–5 were evaluated for their hepatoprotective activities against D-galactosamine-induced toxicity in WB-F344 cells with bicyclol as positive control. As a result, compounds 1 and 2 exhibited moderate hepatoprotective activities. [ABSTRACT FROM AUTHOR]

A new auronolignan derivative, named 6-hydroxy-7′-(4′′-hydroxyphenyl)-10′-acetylauronolignan (1), together with two known auronolignan derivatives (2, 3) were isolated from Cucumis bisexualis for the first time. Their structures were established on the basis of extensive spectroscopic analyses and reported references. Compounds 1–3 were evaluated for their in vitro inhibitory activities against the increase in AST and ALT levels in H2O2-induced HepG2 cells within the range of their maximum nontoxic concentration. Among them, compounds 1 and 2 exhibited moderate hepatoprotective activities. [ABSTRACT FROM AUTHOR]

A new coumarin-xanthone derivative, named 1,3-dihydroxy-2-methoxy-6′-(11′,12′-dimethylchromene-4′,5′-coumarin)-7′′-(4′′-hydroxybenzyl)-10-methylenexanthone (1), along with five known coumarin or xanthone derivatives 2–6 were isolated from Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih for the first time. Their structures were elucidated by their comprehensive spectroscopic data and reported references. Compounds 1–6 were evaluated for their hepatoprotective activities on human L-02 cells in vitro with Bifendatatum as the positive control. Among them, compounds 1, 2, and 6 exhibited moderate promotive effects on the proliferation of L-02 cells and certain hepatoprotective effects on CCl4-induced injury of L-02 cells. [ABSTRACT FROM AUTHOR]

A new geranylated lignan, named 8′-geranylated lignan A (1), and a known lignan (2) were isolated from Oenanthe javanica (Blume) DC., to our knowledge, for the first time. Compounds 1 and 2 were determined by analyzing their extensive spectral data and comparing them with related references. Compounds 1 and 2 exhibited anti-inflammatory activities with IC50 values of 15.24 ± 0.39 μM and 20.07 ± 0.54 μM, which displayed stronger NO inhibitory activities than the positive control (L-NMMA, IC50 = 44.52 ± 0.71 μM). [ABSTRACT FROM AUTHOR]

A new C19-diterpenoid alkaloid, named 17-acetylaconitine A (1), was isolated from salted Aconiti lateralis Radix Praeparata. The structure of compound 1 was elucidated by 1D and 2D NMR, HR-ESI-MS, IR, and related references. Compound 1 exhibited moderate neuroprotective activity with IC50 value of 4.51 μM, which was evaluated for its neuroprotective activity against 6-OHDA-induced cell death in SH-SY5Y cells with curcumin as positive control. [ABSTRACT FROM AUTHOR]

A new lignan, named 1-phenylpropenoate-4,8′-lignan A (1), and three known lignans (2–4) were isolated from Oenanthe javanica (Blume) DC. for the first time. The structures of compounds 1–4 were determined by extensive spectroscopic data analysis and comparison with reported references. Compounds 1–4 were evaluated for their inhibitory activity against LPS-induced NO production in RAW264.7 cells. Among them, compounds 1 and 2 showed certain anti-inflammatory activities with IC50 values of 4.09 ± 0.52 and 6.24 ± 0.64 mM, respectively. [ABSTRACT FROM AUTHOR]

A previously undescribed anthraquinone-aurone adduct 1, named 8-(4′-hydroxy-3′,5′-dimethoxyphenyl)-12-hydroxy-7-(6′′,7′′-dimethylfuran-2′′-one)-9,16-anthraquinone-furochromene-3,2′′-dione, was isolated from the fruits of Cucumis bisexualis. Its structure was determined by comprehensive spectroscopic data and references. Compound 1 was evaluated for its inhibitory effect against the increase in AST and ALT levels in H2O2-induced HepG2 cells in the range of their maximum nontoxic concentration. Compound 1 exhibited moderate hepatoprotective activities in vitro. [ABSTRACT FROM AUTHOR]

A new anthraquinone, named 1,3-dihydroxy-2-methylene-(1′-isopentyloxy)-6-methoxymethyl-8-(6′′,7′′,8′′- trihydroxyphenylketonyl)-9,10-anthraquinone (1), and nine known anthraquinone derivatives (2–10), were isolated from Cucumis bisexualis for the first time. Compounds 1–10 were evaluated for their hepatoprotective activity in human L-O2 cells compared with the positive control bifendatatum. Among them, compounds 1, 3, and 8 exhibited moderate hepatoprotective activity in the proliferation of L-O2 cells. [ABSTRACT FROM AUTHOR]

A new monacolin derivative, namely (1S,2S,5′R,6R,8aR)-7-hydroxy-2,6-dimethyl-8-prenyl-1,2,6,8atetrahydronaphthalene-4′,5′-dihydro-2H-pyran-1′-one (1), and five known monacolin derivatives (2–6) were separated from the highland barley Monascus purpureus Went. for the first time. Their structures were elucidated on the basis of 1D and 2D NMR, HR-ESI-MS, and relevant references. Compounds 1–6 were tested for their hypolipidemic activities by measuring the triglyceride content in HepG2 cells. Among them, compounds 1 and 2 (10 μM) exhibited moderate hypolipidemic activity. [ABSTRACT FROM AUTHOR]

Two new flavones, namely 5-hydroxy-2-(4′-hydroxyphenyl)-6,12,13-trimethoxypyrano-xanthene-4,9-dione (1) and 5-hydroxy-2-(3′-methoxy-4′-hydroxyphenyl)-6-methoxy-11-isopropyl-pyranochromene-4,9-dione (2), were isolated from Salvia plebeia. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR spectral data. Compounds 1 and 2 were evaluated for their anti-angiogenic activities by the MTT assay with axitinib as positive control, and they displayed moderate anti-angiogenic activities with IC50 values of 14.07 and 11.25 μM, respectively. [ABSTRACT FROM AUTHOR]

A new indole alkaloid (1), together with eight known indole alkaloid derivatives (2–9), was isolated from Hosta plantaginea for the first time. The structures of compounds 1–9 were elucidated on the basis of comprehensive spectroscopic analyses and references. Compounds 1–9 were evaluated for their inhibition of steroid 5α-reductase activity in vitro. Among them, compounds 1 and 2 showed important inhibition of steroid 5α-reductase activities. [ABSTRACT FROM AUTHOR]

A new lactone, named 9-allyl-5-methyl-1H-difuro-isochromene-1,8-dione (1), together with nine known lactone derivatives (2–10), was isolated from highland barley Monascus for the first time. Compounds 1–10 were studied by spectroscopic methods and comparison with references and evaluated for their hypolipidemic activities by measuring the triglyceride content in HepG2 cells with simvastatin as positive control. Among them, compounds 1 and 7 (10 μM) exhibited moderate hypolipidemic activities. [ABSTRACT FROM AUTHOR]

Cucumis bisexualis has been widely served as a beneficial wild fruit in China. Four new homoisoflavonoids (1–4), together with eight known homoisoflavonoid derivatives (5–12) were isolated from the 90% EtOH extract of C. bisexualis, using repeated open column chromatography and preparative thin‐layer chromatography. They were elucidated based on the analysis of spectral data and references from the fruits of C. bisexualis for the first time. These compounds (1–12) were evaluated for their in vitro inhibitory effects against the increase of aspartate aminotransferase and alanine aminotransferase levels in H2O2‐induced HepG2 cells in the range of their maximum nontoxic concentration. Among them, compounds 3, 4, 8, and 9 exhibited certain hepatoprotective activities. Practical applications: Cucumis bisexualis A.M. Lu ＆ G.C. Wang is an edible and medical fruit with many functional properties. A detailed study was made to identify the bioactive constituents of C. bisexualis and four new homoisoflavonoids (1–4) and eight known homoisoflavonoid derivatives (5–12) were isolated from the fruits of C. bisexualis for the first time. Compounds 3, 4, 8, and 9 exhibited certain hepatoprotective activities. This study suggests that natural compounds isolated from C. bisexualis could be used as promising hepatoprotective agents. [ABSTRACT FROM AUTHOR]

A new azaanthracene alkaloid, named 1-aza-4-(4′-hydroxybenzyl)-9,10-dimethoxydioxolobenzo-2-oxo-1,2-dihydroanthracene (1), together with seven known azaanthracene alkaloid derivatives (2–8), were isolated from Corydalis decumbens for the first time. Their structures were elucidated by their spectral data and references. Compounds 1–8 were evaluated for their antidepressive activities by inhibiting reuptake of tritiated serotonin ([3H]-NE and [3H]-5-HT) in rat brain synaptosomes. Among them, compounds 1 and 2 showed moderate antidepressive activities. [ABSTRACT FROM AUTHOR]

A new xanthone, named 1,3,5,9-tetrahydroxy-2-prenyl-4-(3′′ -hydroxy-3′′ -methylbutanoyl)-6,6- dimethylpyranoxanthen-10-one (1), along with five known xanthone derivatives (2–6), were isolated from Pyrethrum tatsienense for the first time. Their structures were elucidated on the basis of extensive spectroscopic analysis and references. Compounds 1–6 were screened for their hepatoprotective activities by MTT assay against D-galactosamine induced toxicities in HL-7702 cells, which revealed that compounds 1, 4, and 5 exhibited moderate hepatoprotective activities. [ABSTRACT FROM AUTHOR]

Urtica L. has been long used for gout in traditional Tibetan medicine and is closely related to the effect of reducing uric acid. This study aimed to investigate the effect of Urtica hyperborea Jacq. ex Wedd. (UW) on lowering uric acid and its mechanism by using HK2 cells and hyperuricemia mouse model. Petroleum ether extract (UWP), ethyl acetate extract (UWE), n-butanol extract (UWB), and alcohol-soluble extract (UWA) from UW were prepared, and HK2 cells were treated with various parts extracts to observe the expression of uric acid transporter at 25, 50, and 100 μg/mL for 24 h. Moreover, hyperuricemia mice were administered orally various parts extracts at 0.78 and 2.34 g/kg (crude drug dose converted by extraction rate) to observe the change of hepatic XOD, serum ADA, renal function, and uric acid transporter. In vitro experiments showed that UWA can remarkably elevate OAT1 expression and decrease URAT1 expression in HK2 cells. In vivo experiments showed that UWP, UWE, UWB, and UWA showed remarkable activity in reducing uric acid, rendering a substantial decline in the SUA level in hyperuricemia mice. Compared with the hyperuricemia and allopurinol groups, UWB and UWA had significant protective effects on renal injury. At the same time, UWA can significantly reduce the activity of XOD and ADA, reduce the expression of URAT1, and increase the expression of OAT1. These results indicated that UWA had an outstanding uric acid lowering effect and did not affect renal function. This may be related to increased uric acid excretion and decreased uric acid production, mediated by renal OAT1, URAT1, liver XOD, and serum ADA. UWA may be a potential drug against hyperuricemia. [ABSTRACT FROM AUTHOR]

• Murraya koenigii is not only a condiment, but also a traditional medicinal herb. • Four new phenylpropanoid derivatives (1 – 4), together with eleven known analogues (5 – 15) were isolated from Murraya koenigii. • Compounds 1 , 2 , 6 , and 15 showed inhibitory activities by measuring IL-6-induced STAT3 promoter activities in HepG2 cells. • Compounds 3 , 4 , 9 , 11 , and 14 exhibited inhibitions against LPS-induced NO production in RAW264.7 macrophages. Four new phenylpropanoid derivatives (1 – 4), together with eleven known analogues (5 – 15) were isolated and identified by comparison with their references and extensive spectroscopic methods from Murraya koenigii for the first time. Compounds (1 – 15) were assayed for their inhibitory activities by measuring IL-6-induced STAT3 promoter activities in HepG2 cells, and found compounds 1 , 2 , 6 , and 15 showed inhibitory effects with IC 50 values of 11.5, 18.7, 8.9, and 22.7 μM, respectively. The inhibitory activities of compounds (1 – 15) were screened against NO production in lipopolysaccharide (LPS)-induced RAW264.7 macrophage cells, and found compounds 3 , 4 , 9 , 11 , and 14 exhibited inhibitions against LPS-induced NO production in RAW264.7 macrophages, with IC 50 values of 32.7, 7.9, 42.1, 58.9, and 62.4 μM, respectively. [ABSTRACT FROM AUTHOR]

Two new carbazole alkaloids 1 and 2 , and eleven known congeners 3 – 13 were isolated and identified from Clausena sanki for the first time. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literatures. The compounds 1 – 13 were evaluated by MTT assay to determine whether they decreased VEGF-mediated cell proliferation in HUVECs with Axitinib as positive control. Among them, compounds 1 , 2 , 6 , 8 , and 13 (μM) exhibited moderate antiangiogenic activities, which inhibited VEGF-induced HUVEC proliferation in vitro with IC 50 values of 12.1 (C.I. 8.2–15.2), 58.1 (C.I. 56.3–63.4), 13.7 (C.I. 9.2–15.4), 16.0 (C.I. 9.5–16.4), and 63.2 (C.I. 57.8–65.7) μM, respectively. Moreover, the antiangiogenic activities of compounds 1 – 13 were evidenced in vivo in the zebrafish embryo model. As a result, compounds 1 , 2 , 6 , 8 , and 13 showed effectively suppress angiogenesis. These research results may guide the search for new natural products with antiangiogenic attributes. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Houttuynia cordata is an important traditional Chinese medicine used in heat-clearing and detoxifying, swelling and discharging pus, promoting diuresis and relieving stranguria which recorded in Pharmacopoeia of the people's Republic of China (2015 Edition). H. cordata has been recorded in the book Bencaogangmu which was written by Shizhen Li for the treatment of pyretic toxicity, carbuncle swelling, haemorrhoids, and rectocele diseases. Aim of the study Phytochemical investigation of the aerial parts of H. cordata and evaluation of their PTP1B inhibitory activities and hepatoprotective activities. Materials and methods The dried aerial parts of H. cordata were fractionated by liquid-liquid extraction to obtain CHCl 3 , ethyl acetate, and n-butanolic fractions. The CHCl 3 fraction was confirmed active fraction by the bioactivity-guided investigation, which was isolated and purified by chromatographing over silica gel, Sephadex LH-20, MPLC, and preparative HPLC. The chemical structures of the purified compounds were identified by their spectroscopic data and references. Results Eight new compounds ( 1 – 8 ), together with fourteen known compounds ( 9–22 ) were isolated from the aerial parts of H. cordata. The known compounds ( 9–22 ) were obtained from this plant for the first time. Among them, some compounds exhibited moderate bioactivities. Conclusion Compounds ( 1–8 ) were identified as new alkaloids, and the known alkaloids ( 9–22 ) were isolated from this plant for the first time. Compounds 1 , 4 , 14 , and 19 showed significant PTP1B inhibitory activities with IC 50 values of 1.254, 2.016, 2.672, and 1.862 µm, respectively. Compounds 1 , 3 , 6 , 11 , 17 , and 20 (10 µm) exhibited moderate hepatoprotective activities against D-galactosamine-induced WB-F344 cells damage. [ABSTRACT FROM AUTHOR]

The flower of Hosta plantaginea (Lam.) Aschers (Liliaceae) is a traditional medicinal material in Mongolian medicine for treating sore throat, hoarseness, pulmonary fever, and toxic fever in folk. The present work investigated anti-prostate cancer and hepatoprotective activities of flavonoid derivatives from H. plantaginea (Lam.) Aschers. Aim of the study : To isolate and identify the chemicals of H. plantaginea (Lam.) Aschers for anti-prostate cancer and hepatoprotective activities. Active chemicals were isolated and purified from H. plantaginea (Lam.) Aschers by chromatographic methods, and their structures were established on spectroscopic analysis and references. These compounds were evaluated for their anti-prostate cancer activities using the LNCaP prostate cancer cells, and assayed for their hepatoprotective activities on CCl 4 -induced injury of human L-O2 cells, respectively. Four new flavonol-lignan heterodimers (1 – 4), together with nine known flavonoid derivatives (5 – 13) were isolated from this plant for the first time. Among them, some compounds exhibited moderate anti-prostate cancer and hepatoprotective activities. Compounds 1 , 2 , 5 , and 6 showed anti-prostate cancer activities using the LNCaP prostate cancer cells with IC 50 values of 17.84, 33.26, 54.13, and 81.55 μg/mL, and compounds 3 , 4 , 8 , and 9 exhibited moderate hepatoprotective activities, respectively. A preliminary structure-activity relation was summarized in this paper. Image 1 [ABSTRACT FROM AUTHOR]

• Nine new flavonoids derivatives (1 – 9) were isolated from Heleocharis dulcis. • Neuroprotective and hepatoprotective activities of compounds (1 – 25) were assayed. • Structure-effectiveness relationship was found and discussed scientifically. Chinese water chestnut, the bulb of Heleocharis dulcis , has been widely consumed as fruit or vegetable in China since ancient times. It exhibits health-promoting properties that leads to an extensive study of their active components. Successive chromatography of active fragments of H. dulcis resulted in isolation of five new chalcone-flavonone heterodimers (1 – 3 , 6 , 9), four new diverse flavonoids (4 , 5 , 7 , 8), and sixteen known flavonoids derivatives (10 – 25) were elucidated on the basis of their IR, UV, NMR, MS spectrometry data analysis and references from H. dulcis for the first time. Among these isolates, compounds 4 , 7 , 9 , 12 , 13 , and 17 showed moderate neuroprotective activity, which increased the cell survival rate from 49.23 ± 3.68% for the model to 67.75 ± 2.75%, 57.83 ± 2.46%, 67.98 ± 2.74%, 58.65 ± 3.43%, 56.14 ± 1.99%, and 56.70 ± 1.38% at 10 μM, respectively. Moreover, compounds 1 – 3 , 15 , 16 , 18 , and 20 were found to moderately improve the HepG2 cell survival rates from 39.53% (APAP, 10 mM) to 45.53–53.44%. The outcome of the study provided crucial information regarding the structural diversity and health benefits of the edible bulbs of H. dulcis. [ABSTRACT FROM AUTHOR]

Six lignans (1-6) were isolated from salted Aconiti lateralis Radix Praeparata for the first time. These isolates were elucidated as hedyotisol-A (1), (7″ R ,8″ R)-8″-syringaresinol-4″-hydroxy-3″,5″-dimethoxyphenyl-7″,9″-propanediol (2), lariciresinol-4-O-β - d -glucopyranoside (3),(7 S ,8 S)-4-hydroxy-3-methoxy-7,8-(2′,1′-O-β - d -glucopyranosyl)phenyl-propanetriol (4), (+)-isolariciresinol (5), and (+)-lyoniresinol (6) by analyzing extensive and comprehensive spectral data and compared with the data described in the literature, respectively. Compounds (1-6) were evaluated for their neuroprotective activities against corticosterone-induced cell death in PC12 cells with desipramine as the positive control drug. Among them, compounds 1 and 2 showed moderate neuroprotective activities, which increased the survival rates of PC12 cells from 45.50 ± 2.23% to 65.98 ± 1.29%, 58.19 ± 2.94% at 10 µ m , respectively. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a chronic, progressive brain degenerative disease that is common in the elderly. So far, there is no effective treatment. The multi-target-directed ligands (MTDLs) strategy has been recognised as the most promising approach due to the complexity of the pathogenesis of AD. Herein, novel salicylic acid–donepezil–rivastigmine hybrids were designed and synthesised. The bioactivity results exhibited that 5a was a reversible and selective eqBChE inhibitor (IC50 = 0.53 μM), and the docking provided the possible mechanism. Compound 5a also displayed potential anti-inflammatory effects and significant neuroprotective effect. Moreover, 5a exhibited favourable stabilities in artificial gastrointestinal solution and plasma. Finally, 5a demonstrated potential cognitive improvement in scopolamine-induced cognitive dysfunction. Hence, 5a was a potential multifunctional lead compound against AD. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Lagopsis supina has been used as a traditional medicinal herb for centuries in China. In folk medicine, it is used for promoting blood circulation and removing blood stasis (PBCRBS), anti-inflammatory and diuretic activities. Modern pharmacological investigation have shown that L. supina have an improvement in blood and lymphatic microcirculation, myocardioprotective, and antioxidative activities. Although the pharmacological research of L. supina was more, there was no report on the diuretic activity. Aim of the study This study was to evaluate the diuretic activity and the underlying mechanism of an ethanol extract of L. supina (LS) in a rat model of traumatic blood stasis (TBS). Materials and methods There were 30 male Sprague-Dawley rats that were randomly assigned to the control group, TBS group, and LS group (10 animals in each group). LS was administered orally (460 mg/kg) once daily for 7 successive days. The control group and TBS group were given an equal amount of 0.3% sodium carboxymethyl cellulose (CMC-Na). For the efficacy evaluation, the urine output volume, the urinary electrolyte concentrations (Na+, K+, Cl- and Ca2+) and pH value, the levels of angiotensin II (Ang II), atriopeptin (ANP), anti-diuretic hormone (ADH) and aldosterone (ALD), as well as aquaporin (AQP)-1, 2 and 3 protein expressions were detected in a rat model of TBS. The protein expressions of AQP-1, 2 and 3 were detected by quantitative immunohistochemistry (IHC) and Western blot analysis. Results In the efficacy evaluation, rat models treated with LS showed a significant increase in the total urine output (p < 0.01). The urinary electrolyte and the acid-base disturbances, including the decrease of Na+ and Ca2+ levels and the Na+/K+ value together with the increase in the Cl- level and the pH value, in the urine of the LS group were compared with the TBS group. Moreover, the levels of Ang II, ADH and ALD of rat model were decreased after being treated with LS (p < 0.05 or p < 0.01), while the ANP level was increased (p < 0.05). In addition, the results of the quantitative IHC and the Western blot analysis showed that the expression levels of AQP-1, 2 and 3 proteins decreased significantly compared with those of the TBS group. Conclusions This is the first reported notable diuretic effect by LS, which probably was through the suppression of the renin-angiotensin-aldosterone system (RAAS) and the regulation of the signaling pathways of AQP-1, 2 and 3 protein expressions. Based on our results, we conclude that L. supina carries out its diuretic effect mainly by down-regulating the levels of AQP-1, 2 and 3 expressions in TBS rat model. These data also embody the traditional Chinese medicine (TCM) application principle of Huo xue li shui. These findings suggest that LS may warrant further evaluation as a possible agent for the diuretic drug in clinical applications. Further research is underway to elucidate the active compounds responsible for the diuretic activity of LS. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Sea buckthorn (Hippophae rhamnoides L.) is an important plant with homology of medicine and food. It has rich nutritional and medicinal properties. It is used as a traditional Chinese medicine with therapeutic functions of invigorating spleen, relieving cough, eliminating food, eliminating phlegm, dispersing blood stasis, and promoting blood circulation. This review comprehensively summarized flavonoids from sea buckthorn (Hippophae rhamnoides L.), including extraction methods (solvent extraction, ultrasound-assisted extraction, microwave-assisted extraction, enzyme-assisted extraction, and collaborative extraction), two structure types (18 flavone aglycones and 81 flavone glycosides), detection methods (UV, HPLC, and NMR), bioactivities (antiviral, anti-inflammatory, hepatoprotective, weight-reducing, and hypoglycemic activities), and physiological metabolisms (most of flavonoids are converted into small molecule monophenolic acids through intestinal microbial catabolism). It will supply an important theoretical basis and valuable reference for researching and exploiting sea buckthorn (Hippophae rhamnoides L.) in the future. Practical Applications. Sea buckthorn (Hippophae rhamnoides L.) is an edible and medical plant with many functional properties. A comprehensive review on extraction, structure, detection, bioactivity, and metabolism of flavonoids from sea buckthorn (Hippophae rhamnoides L.) was made in this paper. This review will provide an important foundation for further studies of sea buckthorn (Hippophae rhamnoides L.) focusing on its development and utilization. [ABSTRACT FROM AUTHOR]

The EtOAc soluble fraction showed potential anti-inflammatory activity according to the screening results of the bioactivity-guided investigation. Compounds ( B 1-13 b ) were assayed for their anti-inflammatory activity against NO production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells I in vitro i . Therefore, the EtOAc soluble part was subjected to silica gel column chromatography (100-200 mesh) eluting with a gradient of petroleum ether-EtOAc (12:1, 9:1, 6:1, 3:1) to yield four fractions (Frs. Compounds B 1-13 b were assayed for anti-inflammatory activity against NO production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells I in vitro i . [Extracted from the article]

Lagopsis supina is a well-known traditional Chinese medicine and used as an agent for diuresis in China for centuries. This is the first time to evaluate the diuretic activity of the ethanol extract of L. supina (LS) and its four fractions (LSA, LSB, LSC, and LSD) in normal rats. After the administration of LS-H, LS-M, LSB-H, and LSC-L, the urine output of the rats was significantly increased, while the urine excretion was significantly reduced after treatment with LSB-L. The urine Na+ excretion was remarkably increased with LS-H, LS-M, LSA-H, LSA-L, LSB-H, LSC-L, and LSD-L, and the urine K+ excretion was significantly increased after administration of LS-H and LSB-H. Moreover, the urine Na+ and K+ excretion was significantly reduced after treatment with LSC-H and LSD-H. However, the urine pH values and urine and serum Na+-K+-ATPase levels did not show remarkable change after administration of LS or its four fractions in comparison with the control group. On the contrary, LS and its four fractions can suppress the renin-angiotensin-aldosterone system (RAAS), including ADH arrest by LSB-H, LSB-L, LSC-L, LSD-L, and LSD-H and ALD arrest by LSD-L, as well as promote ANP release by LS-M, LSB-H, LSC-H, and LSD-H, while furosemide can suppress only arrest of ADH within 24 h compared with the control group. In addition, LS and its four fractions did not change the urine and serum TNF-α and IL-6 levels in normal rats within 24 h. This study will provide a quantitative basis for explaining the natural medicinal use of LS as a diuretic agent for edema and promoting the diuretic process. [ABSTRACT FROM AUTHOR]

Targeting WT MLL for the treatment of MLL-r leukemia, which is highly aggressive and resistant to chemotherapy, has been shown to be a promising strategy. However, drug treatments targeting WT MLL are lacking. We used an in vitro histone methyltransferase assay to screen a library consists of 592 FDA-approved drugs for MLL1 inhibitors by measuring alterations in HTRF signal and found that Piribedil represented a potent activity. Piribedil specifically inhibited the proliferation of MLL-r cells by inducing cell-cycle arrest, apoptosis and myeloid differentiation with little toxicity to the non-MLL cells. Mechanism study showed Piribedil blocked the MLL1-WDR5 interaction and thus selectively reduced MLL1-dependent H3K4 methylation. Importantly, MLL1 depletion induced gene expression that was similar to that induced by Piribedil and rendered the MLL-r cells resistant to Piribedil-induced toxicity, revealing Piribedil exerted anti-leukemia effects by targeting MLL1. Furthermore, both the Piribedil treatment and MLL1 depletion sensitized the MLL-r cells to doxorubicin-induced apoptosis. Our study support the hypothesis that Piribedil could serve as a new drug for the treatment of MLL-r AML and provide new insight for further optimization of targeting MLL1 HMT activity. [ABSTRACT FROM AUTHOR]

Aspirin is associated with a reduced risk of cancer and delayed progression of malignant disease. Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-mTOR signaling is believed to partially contribute to these anticancer effects, although the mechanism is unclear. In this study, we revealed the mechanism underlying the effects of aspirin on AMPK-mTOR signaling, and described a mechanism-based rationale for the use of aspirin in cancer therapy. We found that aspirin inhibited mTORC1 signaling through AMPK-dependent and -independent manners. Aspirin inhibited the AMPK-TSC pathway, thus resulting in the suppression of mTORC1 activity. In parallel, it directly disrupted the mTOR-raptor interaction. Additionally, the combination of aspirin and sorafenib showed synergetic effects via inhibiting mTORC1 signaling and the PI3K/AKT, MAPK/ERK pathways. Aspirin and sorafenib showed synergetic anticancer efficacy in the SMMC-7721 model. Our study provides mechanistic insights and a mechanism-based rationale for the roles of aspirin in cancer treatment. [ABSTRACT FROM AUTHOR]

The article reports on obtaining Phenylethanoid glycosides from Houttuynia cordata Thunb., belonging to the Saururacea family. H. cordata has antiviral, anti-inflammatory, and immunostimulating activities. This study isolates and identifies 13 compounds as phenylethanoid glycosides on the basis of extensive spectroscopic analysis.

Approximately 20% of multiple myeloma (MM) are caused by a chromosomal translocation t (4; 14) that leads to the overexpression of the nuclear receptor binding SET domain-protein 2 (NSD2) histone methyltransferase. NSD2 catalyzes the methylation of lysine 36 on histone H3 (H3K36me2) and is associated with transcriptionally active regions. Using high-throughput screening (HTS) with biological analyses, a series of 5-aminonaphthalene derivatives were designed and synthesized as novel NSD2 inhibitors. Among all the prepared compounds, 9c displayed a good NSD2 inhibitory activity (IC 50 = 2.7 μM) and selectivity against both SET-domain-containing and non-SET-domain-containing methyltransferases. Preliminary research indicates the inhibition mechanism of compound 9c by significantly suppressed the methylation of H3K36me2. Compound 9c specifically inhibits the proliferation of the human B cell precursor leukemia cell line RS4:11 and the human myeloma cell line KMS11 by inducing cell cycle arrest and apoptosis with little cytotoxicity. It has been reported that the anti-cancer effect of compound 9c is partly achieved by completely suppressing the transcriptional activation of NSD2-targeted genes. When administered intraperitoneally at 25 mg/kg, compound 9c suppressed the tumor growth of RS4:11 xenografts in vivo and no body weight loss was detected in the tested SCID mice. [Display omitted] • 5-aminonaphthalene derivatives were designed, synthesized and evaluated, the SAR of these compounds was demonstrated. • Compound 9c exhibited a good NSD2 inhibitory activity and inhibited the proliferation of leukemia cell line. • The anti-cancer effect of 9c is partly achieved by suppressing the transcriptional activation of NSD2-targeted genes. • When administered intraperitoneally at 25 mg/kg, compound 9c suppressed the tumor growth of RS4:11 xenografts in vivo. [ABSTRACT FROM AUTHOR]

Here we reported novel apigenin-rivastigmine hybrids were rationally designed and synthesized by the multi-target-directed ligands (MTDLs) strategy, their activity in vitro results revealed that compound 3d showed significant antioxidant potency (ORAC = 1.3 eq), and it was a reversible hu AChE (IC 50 = 6.8 μM) and hu BChE (IC 50 = 16.1 μM) inhibitor. 3d also served as a selective metal chelator, and it significantly inhibited and disaggregated self-mediated and Cu2+-mediated A β 1-42 aggregation, and also inhibited h AChE-mediated induced A β 1-40 aggregation. Compound 3d exhibited remarkable neuroprotective effect and hepatoprotective activity. In addition, compound 3d presented favourable blood-brain barrier penetration in vitro and drug-like property. Further, the in vivo assay displayed that 3d indicated remarkable dyskinesia recovery rate and response efficiency on AD zebrafish, and exhibited surprising protective effect on A β 1-40 -mediated zebrafish vascular injury. More importantly, 3d did not indicate obvious acute toxicity at dose up to 2000 mg/kg, and could improve scopolamine-induced memory impairment. Subsequently, the regulation of multi-targets for 3d were further confirmed through transcriptome sequencing of brain hippocampi, which also offered novel potential targets and opened a new way to treat Alzheimer's disease. More interestingly, the metabolism of 3d in vitro indicated that 4 metabolites in rat liver microsome metabolism, 2 metabolites in human liver microsome metabolism, and 4 metabolites in intestinal flora metabolism, which offered supports for the preclinical study of 3d. Overall, this study exhibited that compound 3d was a promising advanced compound targeted multiple factors associated with AD. Image 1 • Novel apigenin-rivastigmine hybrids was rationally designed. • 3d was a promising multi-function agent. • 3d could improve AlCl 3 -induced zebrafish AD. • 3d could protect A β 1-40 -mediated zebrafish vascular injury. • 3d could improve scopolamine-induced memory impairment. [ABSTRACT FROM AUTHOR]

Summary Mutations or aberrant upregulation of EZH2 occur frequently in human cancers, yet clinical benefits of EZH2 inhibitor (EZH2i) remain unsatisfactory and limited to certain hematological malignancies. We profile global posttranslational histone modification changes across a large panel of cancer cell lines with various sensitivities to EZH2i. We report here oncogenic transcriptional reprogramming mediated by MLL1’s interaction with the p300/CBP complex, which directs H3K27me loss to reciprocal H3K27ac gain and restricts EZH2i response. Concurrent inhibition of H3K27me and H3K27ac results in transcriptional repression and MAPK pathway dependency in cancer subsets. In preclinical models encompassing a broad spectrum of EZH2-aberrant solid tumors, a combination of EZH2 and BRD4 inhibitors, or a triple-combination including MAPK inhibition display robust efficacy with very tolerable toxicity. Our results suggest an attractive precision treatment strategy for EZH2-aberrant tumors on the basis of tumor-intrinsic MLL1 expression and concurrent inhibition of epigenetic crosstalk and feedback MAPK activation. Graphical Abstract Highlights • Epigenetic signature profiling in ∼100 tumor lines with different EZH2i sensitivities • MLL1-p300/CBP-mediated H3K27ac gain and oncogenic reprogramming limit EZH2i response • H3K27ac co-inhibition improves EZH2i efficacy but activates MAPK in some cancers • MLL1 level and inhibiting feedback MAPK activation expand EZH2i utility and precision Epigenetic crosstalk targeting together with MLL1-based stratification and inhibiting feedback MAPK activation expand EZH2 inhibitors’ therapeutic utility and efficacy in patient-derived solid tumor models. [ABSTRACT FROM AUTHOR]