Chemical Constituents from Berchemia polyphylla var. Leioclada.

One previously undescribed naphthoquinone-benzisochromanquinone dimer berpolydiquinone A (1), along with two previously undescribed naphthoquinone-anthraquinone dimers berpolydiquinones B and C (2-3), and one previously undescribed dimeric naphthalene berpolydinaphthalene A (4), were isolated from the stems and leaves of Berchemia polyphylla var. leioclada. The chemical structures of these compounds were determined using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS), spectroscopic data, the exciton chirality method (ECM), and quantum chemical calculation. Notably, compounds (1-2 and 5) are dimeric quinones that share the same naphthoquinone moiety, specifically identified as 2-methoxystypandron. Compound (4) is a derivative of dimeric naphthalene with a symmetrical structure, which is a new structure type isolated from B. polyphylla var. leioclada for the first time. These findings suggest that B. polyphylla var. leioclada serves as a significant reservoir of structurally diverse phenolic compounds. This study provides a scientific foundation for regarding B. polyphylla var. leioclada as a potential source of "Tiebaojin".

Anthraquinone-benzisochromanquinone dimers from the stems and leaves of Berchemia polyphylla.

Three new anthraquinone-benzisochromanquinone dimers polyphylldiquinones A-C (1-3), along with three known analogs floribundiquinone A-B (4-5) and 7-dehydroxyventiloquinone H (6), were isolated from the stems and leaves of Berchemia polyphylla. The chemical structures and absolute configurations of these compounds were determined using HR-ESI-MS, spectroscopic data, and electronic circular dichroism. Notably, compounds (1-5) are dimeric quinones that share the same benzisochromanquinone moiety, specifically identified as 7-dehydroxyventiloquinone H (6), which was the first time to report as a natural product. Compounds 1-2 and compounds 4-5 are two pairs of atropisomers respectively.

Phenolic Compounds From the Stems and Leaves of Berchemia lineata (L.) DC.

Eight new phenolic compounds, named bercheminols A-H (1-8), and eleven known analogues were isolated from the stems and leaves of Berchemia lineata (L.) DC. Their structures including the absolute configurations were elucidated by extensive spectroscopic analysis, chemical method, and quantum chemical calculations. Compound 1 possesses an unprecedented 3,4-dihydro-11H-benzo[b]pyrano[4,3-e] oxepin-11-one skeleton. The other new compounds belong to three structural types of natural products, including naphthopyrones (2-5), flavonoids (6-7), and bibenzyl (8). The α-glucosidase inhibitory activities of the isolated compounds were assayed. As a result, vittarin-B (9), rubrofusarin-6-O-ß-D-glucopyranoside (11), quercetin (14), kaempferol (15), and dihydrokaempferol (17) showed moderate inhibitory activities against α-glucosidase with IC50 values of 22.5, 28.0, 36.5, 32.7, and 31.9 µM, respectively.

Two novel cyclohexanone-monocyclic polycyclic polyprenylated acylphloroglucinols from Garcinia multiflora fruits.

Two novel cyclohexanone-monocyclic polyprenylated acylphloroglucinol (C-MPAP) derivatives, named norgarmultinones A (1) and B (2), were isolated from the fruits of Garcinia multiflora. Their structures were clarified by NMR, HRESIMS and calculated electronic circular dichroism (ECD) spectra. Compound 2 is the first example of naturally occurring C-MPAPs containing tetrahydropyran moiety by the cyclization of an enolic hydroxyl with an isogeranyl side chain. The reasonable biosynthetic routes of 1 and 2 were also put forward.

Aralia armata (Wall.) Seem Improves Intimal Hyperplasia after Vascular Injury by Downregulating the Wnt3α/Dvl-1/ß-Catenin Pathway.

The aim of the study is to examine the mechanism of Aralia armata (Wall.) Seem (AAS) in improving intimal hyperplasia after vascular injury in rats. Rats with femoral artery injury were randomly divided into three groups: the model group, AAS low-dose group (40 mg/kg), and AAS high-dose group (80 mg/kg). The sham operation group was used as a control group. HE staining was used to observe the changes in femoral artery vessels. Immunohistochemistry was adopted to detect α-SMA, PCNA, GSK-3ß, and ß-catenin proteins in femoral artery tissue. The CCK-8 test and wound healing assay were employed to analyze the effect of AAS on proliferation and migration of vascular smooth muscle cells (VSMCs) cultured in vitro. Western blotting (WB) and polymerase chain reaction (PCR) assays were used to evaluate the molecular mechanism. AAS reduced the stenosis of blood vessels and the protein expressions of α-SMA, PCNA, GSK-3ß, and ß-catenin compared to the model group. In addition, AAS (0-15 µg/mL) effectively inhibited the proliferation and migration of VSMCs. Moreover, the results of WB and PCR showed that AAS could inhibit the activation of ß-catenin induced by 15% FBS and significantly decrease the expression levels of Wnt3α, Dvl-1, GSK-3ß, ß-catenin, and cyclin D1 in the upstream and downstream of the pathway. AAS could effectively inhibit the proliferation and migration of neointima after vascular injury in rats by regulating the Wnt/ß-catenin signaling pathway.

Inhibition of HDAC4 by GSK3ß leads to downregulation of KLF5 and ASK1 and prevents the progression of intravertebral disc degeneration.

BACKGROUND: Intervertebral disc degeneration (IDD) is a major cause of lower back pain. This study aimed at exploring the effects of histone deacetylase 4 (HDAC4) and its upstream and downstream signaling molecules on IDD development. METHODS: A murine IDD model was established by inducing a needle puncture injury to the vertebrate, whereupon we isolated and transfected of nucleus pulposus (NP) cells. Disc height index (DHI) of the mice was determined by X-ray tomography, while the pain experienced by the IDD mice was evaluated by mechanical and thermal sensitivity tests. Next, the interaction between GSK3ß and HDAC4 as well as that between HDAC4 and KLF5 acetylation was assessed by co-immunoprecipitation, while the promoter region binding was assessed identified by chromatin immunoprecipitation. By staining methods with TUNEL, Safranin O fast green, and hematoxylin and eosin, the NP cell apoptosis, degradation of extracellular matrix, and morphology of intervertebral disc tissues were measured. Furthermore, mRNA and protein expressions of GSK3ß, HDAC4, KLF5, and ASK1, as well as the extent of HDAC4 phosphorylation, were determined by RT-qPCR and Western blotting. RESULTS: GSK3ß was identified to be downregulated in the intervertebral disc tissues obtained from IDD mice, while HDAC4, KLF5, and ASK1 were upregulated. HDAC4 silencing alleviated IDD symptoms. It was also found that GSK3ß promoted the phosphorylation of HDAC4 to increase its degradation, while HDAC4 promoted ASK1 expression through upregulating the expression of KLF5. In IDD mice, GSK3ß overexpression resulted in increased DHI, inhibition of NP cell apoptosis, alleviation of disc degeneration, and promoted mechanical and thermal pain thresholds. However, HDAC4 overexpression reversed these effects by promoting ASK1 expression. CONCLUSION: Based on the key findings of the current study, we conclude that GSK3ß can promote degradation of HDAC4, which lead to an overall downregulation of the downstream KLF5/ASK1 axis, thereby alleviating the development of IDD.

Acylphloroglucinol and tocotrienol derivatives from the fruits of Garcinia paucinervis.

Three undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) and three tocotrienols derivatives, named as paucinochymol A-F (1-3 and 10-12), together with six known PPAPs, were isolated from the fruits of Garcinia paucinervis. Their structures and absolute configurations were determined by extensive NMR analysis and electronic circular dichroism (ECD) calculation methods. Paucinochymol A (1) is the first compound of this type featuring a ω-isogeranyl with tetrahydrofuran unit at C-1. Paucinochymols D and E (4-5) belong to rare tocotrienol with one glorious macrocyclic and an ortho-quinone moiety, respectively. The antiproliferative and anti-inflammatory activities of all isolates were tested. Four PPAPs exhibited weak inhibitory activities against three human cancer cell lines (HepG2, T98, MCF-7) with IC50 values ranging from 10.0 to 16.0 µM. Paucinochymol D (10) displayed moderate inhibitory effects against nitric oxide (NO) production with the IC50 value of 19.8 µM.

Extracellular vesicles derived from microRNA-150-5p-overexpressing mesenchymal stem cells protect rat hearts against ischemia/reperfusion.

An intriguing area of research has demonstrated the ability of extracellular vesicles (EVs) as biological vehicles for microRNAs (miRNAs) transfer. Mesenchymal stem cells (MSCs) produce large amounts of EVs. Rat models of ischemia/reperfusion (I/R) were established to explore the expression profile of thioredoxin-interacting protein (TXNIP), which was then knocked-down to investigate its effects on myocardial remodeling, followed by detection on myocardial infarction size (MIS), myocardial collagen volume fraction (CVF) and cardiomyocyte apoptosis. MSCs-derived EVs carrying miR-150-5p were cultured with neonatal cardiomyocytes under hypoxia/hypoglycemia condition for in vitro exploration and intramyocardially injected into I/R rats for in vivo exploration. I/R-induced rats presented higher TXNIP levels and lower miR-150-5p levels, along with increased cardiomyocyte apoptosis. miR-150-5p in MSCs was transferred through EVs to cardiomyocytes, leading to suppressed myocardial remodeling, as reflected by smaller MIS and CVF and suppressed cardiomyocyte apoptosis. I/R-treated rats injected with MSCs-derived EVs containing miR-150-5p showed a reduction in myocardial remodeling associated with the downregulation of TXNIP, which may be clinically applicable for treatment of I/R.

Anti-inflammatory and antiproliferative prenylated sulphur-containing amides from the leaves of Glycosmis pentaphylla.

Glycosmis pentaphylla (Retz.) DC (Rutaceae) has been traditionally considered as anti-cancer and anti-inflammatory medicine. However, active compounds of sulphur-containing amides remain largely unknown. In the present work, eighteen previously undescribed sulphur-containing amides (1-18) and three known analogues (19-21) were isolated from the leaves of G. pentaphylla. Their structures were elucidated by NMR spectroscopy and mass spectrometry. All isolated prenylated sulphur-containing amides were evaluated for their anti-inflammatory properties together with antiproliferative activities in vivo. Prenylated sulphur-containing amides exhibited significant inhibitory effects against nitric oxide (NO) production stimulated by lipopolysaccharide in mouse macrophage RAW 264.7 cells with the IC50 values ranging from 0.16 ± 0.10 to 16.74 ± 2.81 µM. Meanwhile, sulphur-containing amides also exhibited considerable antiproliferative activities against HepG2 cell line with IC50 values ranging from 7.47 ± 0.91 to 16.23 ± 0.80 µM. These findings enrich and improve the research on the structural diversity and biological activity of sulphur-containing amides and provide phytochemical and pharmacological evidence for the further development and utilization of the leaves of G. pentaphylla in pharmaceutical industry.

Medicated thread moxibustion for alopecia areata: A case report.

RATIONALE: According to the literature reports and clinical studies on alopecia areata (AA) from 2008 to 2018, most clinical treatments have been oral drugs and external ointments. At present, systemic immunosuppressive therapy has been widely used in AA, but there are various side effects such as elevated liver enzymes, gastrointestinal discomfort, poor drug compliance, and repeated illness. We present a case report describing a traditional medicine treatment for AA that uses an ethnic therapy of Zhuang medicine, a kind of Traditional Chinese Medicine, namely, medicated thread moxibustion. PATIENT CONCERNS: A 36-year-old man endured AA after going through a family misfortune. Half a year ago, his father passed away suddenly. Since then, he suffered continuous anguish, alcoholism and hair loss, especially in the past 2 months. A coin-shaped area of hair loss began to appear at the top of his head and gradually expanded to the surrounding region. DIAGNOSES: A diagnosis of AA was made in the dermatology department of a local hospital. INTERVENTIONS: The patient was treated with the medicated thread moxibustion method of Traditional Zhuang Medicine at the Kuihua (special points of Zhuang medicine), Zusanli (ST 36), Xuehai (SP 10), Baihui (DU 20), and Taichong (LR 3) points every other day for 4 weeks. OUTCOMES: The area of hair loss showed slight improvement after 1 week of treatment. Only just a sprinkling of wooly hairs, whose color and thickness were similar to those of fine facial hairs, began to emerge sporadically from the follicles; they could be seen only in a bright light. When the patient saw the obvious curative effect, we continued the treatment for 2 weeks with the patient's consent. Three weeks later, the patchy AA area was covered with small cotton-like hairs of different lengths and uneven colors. LESSONS: The medicated thread moxibustion method of Zhuang medicine can be an effective alternative treatment in patients with AA.

Differentiation of the Chinese minority medicinal plant genus Berchemia spp. by evaluating three candidate barcodes.

The genus Berchemia comprises important Chinese plants with considerable medicinal value; however, these plants are often misidentified in the herbal medicinal market. To differentiate the various morphotypes of Berchemia species, a proficient method employing the screening of universal DNA barcodes was used in this work. Three candidate barcoding loci, namely, psbA-trnH, rbcL, and the second internal transcribed spacer (ITS2), were used to identify an effective DNA barcode that can differentiate the various Berchemia species. Additionally, PCR amplification, efficient sequencing, intra- and inter-specific divergences, and DNA barcoding gaps were employed to assess the ability of each barcode to identify these diverse Berchemia plants authentically; the species were differentiated using the Kimura two-parameter and maximum composite likelihood methods. Sequence data analysis showed that the ITS2 region was the most suitable candidate barcode and exhibited the highest interspecific divergence among the three DNA-barcoding sequences. A clear differentiation was observed at the species level, in which a maximum distance of 0.264 was exhibited between dissimilar species. Clustal analysis also demonstrated that ITS2 clearly differentiated the test species in a more effective manner than that with the two other barcodes at both the hybrid and variety levels. Results indicate that DNA barcoding is ideal for species-level identification of Berchemia and provides a foundation for further identification at the molecular level of other Rhamnaceae medicinal plants.

Three new steroidal glycosides from the roots of Cynanchum auriculatum.

Three new steroidal glycosides, cyanoauriculosides F, G and H (1-3), were isolated from the roots of Cynanchum auriculatum (Asclepiadaceae) along with two known steroidal derivatives. On the basis of spectroscopic analysis and chemical methods, their structures were identified as 20-O-acetyl-8,14-seco-penupogenin-8-one 3-O-α-L-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-α-L-diginopyranosyl-(1→4)-ß-D-cymaropyranoside (1), 2',3'-Z-gagaminine 3-O-α-L-cymaropyranosyl-(1→4)-ß-D-cymaro-pyranosyl-(1→4)-α-L-diginopyranosyl-(1→4)-ß-D-cymaropyranoside (2), 17-O-acetyl-kidjoranin 3-O-α-L-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-α-L-cymaro-pyranosyl-(1→4)-ß-D-digitoxopyranosyl-(1→4)-ß-D-digitoxopyranoside (3), gagaminine 3-O-α-L-cymaropyranosyl-(1→4)-ß-D-cymaropyranosyl-(1→4)-α-L-digino-pyranosyl-(1→4)-ß-D-cymaropyranoside (4) and wilfoside D1N (5).

[The species basis of Berchemia lineata and its drug commodity].

OBJECTIVE: To investigate the original plant, distribution and efficacy of Radix Seu Stem Berchemiae (Tie Bao Jin) in Zhuang Region of Guangxi and southwest China. METHODS: The original plants of Tie Bao Jin were identified by methods of commodity investigation, specimen collection, literature reference and specimens identification. RESULT: The clinical commonly used as Tie Bao Jin original plant in Zhuang Region of Guangxi were identified as the stem and root of Berchemia lineata (L.) DC, Berchemia polyphylla Wall. ex Laws., Berchemia polyphylla Wall. ex Lawson var. leioclada (Hand. -Mazz. ) Hand. -Mazz. and Berchemia floribunda (Wall.) Brongn. CONCLUSION: Actually, the stem and root of the four plants have been used as Tie Bao Jin in southwest China. And their plant resource include their identification, pharmacodynamics action and the clinical difference still need further research.

A new chromone derivative from Berchemia lineata.

To study the chemical constituents from the root of Berchemia lineata (L.) DC., nine compounds were isolated from the EtOAc extract by using silica gel, RP-C18 silica gel column chromatography and preparative HPLC. Based on the spectroscopic analysis, their structures were identified as 5-hydroxy-7-(2'-hydroxypropyl)-2-methyl-chromone (1), (-)-(1'R, 2'S)-erythro-5-hydroxy-7-(1', 2'-dihydroxypropyl)-2-methyl-chromone (2), naringenin (3), eriodictyol (4), (+)-aromadendrin (5), (+)-taxifolin (6), (+)-catechin (7), (+)-epigallocatechin (8) and quercetin (9). Among them, compound 2 is a new chromone derivative. Compound 1 is a known chromone derivative and isolated from this genus for the first time. Compounds 3-9 are known flavonoids and isolated from this plant for the first time.