Uncária Tomentosa (Wild.) D.C. em processos inflamatórios na doença de Alzheimer / Uncária Tomentosa (Wild.) D.C. en procesos inflamatorios en la enfermedad de Alzheimer / Uncária Tomentosa (Wild.) D.C. in inflammatory processes in Alzheimer's disease

Objetivo: explorar os mecanismos envolvidos no desencadeamento e progressão da Doença de Alzheimer (DA) de forma a embasar a sugestão da planta Uncaria Tomentosa (Wild.) como mais uma possiblidade terapêutica coadjuvante para prevenção e tratamento da DA. Método: Trata-se de uma revisão narrativa da literatura realizada com busca de artigos publicados em bases indexadas e diretamente nas revistas de interesse, utilizando-se como descritores "Uncária Tomentosa", "Doença de Alzheimer", e os respectivos termos em inglês. Resultados: com os avanços para a compreensão dos mecanismos moleculares que desencadeiam os efeitos apresentados no desenvolvimento da DA, os diversos mecanismos dos fitocompostos presentes na planta sugerem sua utilização como neuroprotetor, por mecanismos anti-inflamatórios, imunomoduladores e antioxidantes, cujas evidências em literatura são apresentadas para defesa de sua utilização nesta patologia. Conclusão: foram encontradas evidências para sugerir a inclusão da Uncaria tomentosa (Wild.) como possível terapêutica complementar no tratamento da DA. Sua utilização deve ser melhor explorada para aplicação como tratamento complementar as terapêuticas convencionais para a DA

Objective: to explore the mechanisms involved in the triggering and progression of Alzheimer's disease (AD) in order to support the suggestion of the Uncaria Tomentosa (Wild.) plant as another adjuvant therapeutic possibility for the prevention and treatment of AD. Method: This is a narrative review of the literature conducted with a search for articles published on indexed bases and directly in the journals of interest, using as descriptors "Uncária Tomentosa", "Alzheimer's disease", and the respective terms in English. Results: with advances to understand the molecular mechanisms that trigger the effects presented in the development of AD, the various mechanisms of phytocompounds present in the plant suggest its use as neuroprotector, by anti-inflammatory, immunomodulatory and antioxidant mechanisms, whose evidence in the literature is presented to defend its use in this pathology. Conclusion: evidence was found to suggest the inclusion of Uncaria tomentosa (Wild.) as a possible complementary therapy in the treatment of AD. Its use should be better explored for application as a complementary treatment to conventional therapies for AD.

Objetivo: explorar los mecanismos implicados en el desencadenamiento y progresión de la enfermedad de Alzheimer (EA) con el fin de apoyar la sugerencia de la planta Uncaria Tomentosa (silvestre) como otra posibilidad terapéutica adyuvante para la prevención y tratamiento de la EA. Método: Se trata de una revisión narrativa de la literatura realizada con una búsqueda de artículos publicados en bases indexadas y directamente en las revistas de interés, utilizando como descriptores "Uncária Tomentosa", "Alzheimer's disease", y los términos respectivos en inglés. Resultados: con los avances para comprender los mecanismos moleculares que desencadenan los efectos presentados en el desarrollo de la EA, los diversos mecanismos de fitocompuestos presentes en la planta sugieren su uso como neuroprotector, por mecanismos antiinflamatorios, inmunomoduladores y antioxidantes, cuya evidencia en la literatura se presenta para defender su uso en esta patología. Conclusión: se encontró evidencia que sugiere la inclusión de Uncaria tomentosa (Silvestre) como una posible terapia complementaria en el tratamiento de la EA. Su uso debe explorarse mejor para su aplicación como tratamiento complementario a las terapias convencionales para la EA.

Soil Heavy Metal Content and Enzyme Activity in Uncaria rhynchophylla-Producing Areas under Different Land Use Patterns.

In this study, we investigated the content of soil heavy metals, the level of heavy metal pollution and the characteristics of soil enzyme activity under three different land use patterns of Uncaria rhynchophylla base, forestland and wasteland in Jianhe County, Qiandongnan Prefecture, Guizhou Province, revealing the intrinsic correlation between heavy metal content and soil enzyme activity to reveal the relationship between soil enzyme activity and heavy metal content under different land use patterns in the Uncaria rhynchophylla production area. The results showed that soil Cd and Hg contents in Uncaria rhynchophylla base both exceeded the national soil background value. The single pollution index indicated that Cd had the greatest contribution to Pn, and the comprehensive pollution index (Pn) demonstrated no heavy metal pollution in the soil of Uncaria rhynchophylla-producing areas. Under different land use patterns, the enzyme activity was forestland > wasteland > Uncaria rhynchophylla base, and catalase and acid phosphatase activities presented significant spatial differences (p < 0.05). The correlation between soil enzyme activity and heavy metal content was uncertain due to the changes in land use patterns and heavy metal species. The proportions of positive correlation and negative correlation between soil enzyme activity and heavy metals in Uncaria rhynchophylla base were 50%, respectively. In the forestland, soil enzyme activity was positively correlated with heavy metals, while in the wasteland, soil enzyme activity was negatively correlated with heavy metals. This study revealed that the changes in heavy metal content should be focused on for the soil quality in Uncaria rhynchophylla-producing areas under different land use patterns. The results of the study provide some basic theoretical references for the improvement of soil quality in the production area of Uncaria rhynchophylla under different land use practices.

Characterization and Comparative Analysis of Chloroplast Genomes in Five Uncaria Species Endemic to China.

Uncaria, a perennial vine from the Rubiaceae family, is a typical Chinese traditional medicine. Currently, uncertainty exists over the Uncaria genus' evolutionary relationships and germplasm identification. The complete chloroplast genomes of four Uncaria species mentioned in the Chinese Pharmacopoeia and Uncaria scandens (an easily confused counterfeit) were sequenced and annotated. The findings demonstrated that the whole chloroplast genome of Uncaria genus is 153,780-155,138 bp in full length, encoding a total of 128-131 genes, containing 83-86 protein-coding genes, eight rRNAs and 37 tRNAs. These regions, which include eleven highly variable loci and 31-49 SSRs, can be used to create significant molecular markers for the Uncaria genus. The phylogenetic tree was constructed according to protein-coding genes and the whole chloroplast genome sequences of five Uncaria species using four methods. The topology of the two phylogenetic trees showed no difference. The sequences of U. rhynchophylla and U. scandens are clustered in one group, while the U. hirsuta and U. macrophylla are clustered in another group. U. sessilifructus is clustered together with the above two small clades. New insights on the relationship were revealed via phylogenetic research in five Uncaria species. This study will provide a theoretical basis for identifying U. rhynchophylla and its counterfeits, as well as the species of the Uncaria genus. This research provides the initial chloroplast genome report of Uncaria, contributes to elucidating the chloroplast genome evolution of Uncaria in China.

Current Research of Phytochemical, Medicinal and Non-Medicinal Uses of Uncaria gambir Roxb.: A Review.

Uncaria gambir Roxb. is a plant from Southeast Asia and is widely used as an alternative medicine with various applications. This plant has been widely used in traditional medicine. This paper aims to provide information on U. gambir, a summary of data on phytochemicals and on medical and nonmedical activities. Phytochemical studies reveal biologically active constituents such as flavonoids, phenolics, and alkaloids. Various studies have shown that extracts and compounds obtained from U. gambir have medical uses for their antioxidant, antibacterial, anti-helminthic, anticancer, antifungal, anti-inflammatory, anti-hyperglycemic, anti-hyperuricemic, anti-lipid peroxidation, antihyperlipidemic and other properties. In addition, this extract has other uses, such as adsorbent for dyes and metal ions, as well as corrosion inhibition. Thus, U. gambir, which is commonly used in traditional medicine, is a potential plant for many therapeutic applications and prospects for drug development as well as other applications such as adsorbent and corrosion inhibition.

Environmentally benign cinchonain IIa from Uncaria laevigata for corrosion inhibition of Q235 steel in HCl corrosive medium: Experimental and theoretical investigation.

Traditional corrosion inhibitors make great contribution to metal protection, but also cause environmental pollution. To solve the problem, plant extracts as green corrosion inhibitors have attracted much attention in recent years. Plants are good raw materials for corrosion inhibitors and also meet the requirements of industry. However, they have not been successfully applied in industry due to the unknown composition of the effective corrosion inhibitors and large dosage thereof. Therefore, cinchonain IIa was separated from Uncaria laevigata with abundant sources and low cost from nature in this work. Here we hypothesized that cinchonain IIa could show good corrosion inhibition performance for Q235 steel in the acidic medium. Through experiments and theoretical calculation, we studied the corrosion inhibition effect of cinchonain IIa on Q235 in 1 M HCl solution at 298 K for 48 h. Electrochemical experiments revealed that the inhibition efficiency of 200 mg/L cinchonain IIa in 1 M HCl for Q235 steel was 94.08% for 48 h. It even showed over 93% corrosion inhibition efficiency and durable protection performance to 28 d. Surface observations indicated that cinchonain IIa were firmly attached to the steel surface by forming a protective film. Moreover, quantum chemical calculation and molecular dynamics simulation revealed the inhibition mechanism at molecular and atomic level. Compared with some plant extracts, here we demonstrate that the outstanding advantages of cinchonain IIa include sustained protective effect, small dosage, and low toxicity. Accordingly, it may be used as a green industrial corrosion inhibitor with great potential in oilfield acidification and acid pickling.

GJD Modulates Cardiac/Vascular Inflammation and Decreases Blood Pressure in Hypertensive Rats.

Gedan Jiangya decoction (GJD) (aqueous ethanol extract), a traditional Chinese medicine formula which contain six botanical drugs (Uncaria rhynchophylla (Miq.) Miq., Salvia miltiorrhiza Bunge, Pueraria lobata (Willd.) Ohwi, Eucommia ulmoides Oliv., Prunella vulgaris L., and Achyranthes bidentata Blume) was designed to treat hypertension; however, the underlying mechanism of action is unclear. This study aimed to determine the mechanisms of action of GJD in the treatment of hypertension in spontaneously hypertensive rats (SHR). Male SHRs were randomly divided into five groups: GJD doses were low (1.36 g/kg/d), medium (2.72 g/kg/d), and high (5.44 g/kg/d), captopril (13.5 mg/kg/d), and SHR groups, with Wistar-Kyoto rats (WKY) serving as the control. Every rat was gavaged once a day. The ALC-NIBP, a noninvasive blood pressure device, measured systolic (SBP) and diastolic (DBP) blood pressures. Six weeks following treatment, all rats were anesthetized. The blood samples were obtained from the abdominal aorta and then serum isolated to assess endothelin-1 and angiotensin II, interleukin-1beta, interleukin-6, and TNF-alpha. The left ventricular and thoracic aortas were taken for HE staining, immunohistochemistry, RT-qPCR, and western blot examination. Following GJD therapy, SBP and DBP were significantly lowered, as were serum levels of endothelin-1 and angiotensin II. The thickness of the left ventricular and thoracic aorta walls reduced, as did type I collagen, type III collagen, and alpha-SMA expression in the left ventricular and aortic tissues. The GJD treatment significantly reduced serum levels of the inflammatory markers interleukin-1beta, interleukin-6, and TNF-alpha. Furthermore, interleukin-1 beta, interleukin-6, TNF-alpha, TAK1, and NF-κB/p65 levels were significantly reduced in left ventricular and aortic tissues, whereas IkB-alpha levels were significantly elevated. GJD has a dose-dependent effect on all parameters. In conclusion, GJD has been shown to lower blood pressure, improve cardiovascular remodeling, and reduce inflammation via regulating NF-κB in SHRs.

[Two new monoterpenoid indole alkaloids from hook-bearing branches of Uncaria sessilifructus].

The present study investigated the chemical constituents from Uncaria sessilifructus and their neuroprotective activities. The compounds were separated and purified from the 90% ethanol extract of U. sessilifructus by various chromatographic methods, including silica gel, Sephadex LH-20, and semi-preparative HPLC. Seven compounds were obtained, and their structures were identified as uncanidine J(1), uncanidine K(2), 17-O-ethylhirsutine(3), tetrahydroalstonine(4), akuammigine(5), hirsutine(6), and hirsuteine(7) by physicochemical properties and various spectral techniques, including UV, IR, MS, and NMR. Compounds 1 and 2 are two new compounds. Compound 3 is a new natural product, and compound 4 was isolated from U. sessilifructus for the first time. In addition, the isolated compounds were evaluated for their neuroprotective effects on oxygen and glucose deprivation/reoxygenation(OGD/R) injury in primary cortical neurons in rats. The results showed that compounds 1-7 had different degrees of protective effects on OGD/R injury. The EC_(50) values of compounds 2-4 were(0.17±0.03),(1.70±0.38), and(1.79±0.23) µmol·L~(-1), respectively.

Mechanisms of natural products as potential antiepileptic drugs.

The universal epileptogenic cascade remains unknown and most modern treatments focus on the reduction of symptoms and the prevention of seizure recurrence. Experimental studies have demonstrated that herbal medicines may act as antiepileptogenic agents. In this study, the possibilities of plants with antiepileptic properties were reviewed and discussed on their structures and related mechanism of actions. This work constituted a literature review of medicinal plants showing antiepileptic properties by literature searching in Science Direct, PubMed and Wiley Online Library. The keywords of search included epilepsy, antiepileptogenesis, antiepilepsy, natural compounds, extract, herbal medicines and medicinal plants in epilepsy treatment. Only articles published in English were reviewed. Mechanism of action of the natural plants were described according to experimental studies. From the databases, we found 135 natural plants with antiepileptic properties. In this review, the highly studied natural plants were selected. These included Acorus calamus, Bacopa monnieri, Boerhaavia diffusa, Curcuma longa, Gastrodia elata, Ginseng, Uncaria rhynchophylla, Pinellia ternatae, Withania somnifera, Magnolia bark and Resveratrol-related products. From the evidences, natural products may potentially be developed as antiepileptic or antiepileptogenic agents. However, several issues in drug development should be considered such as safety, formulations, pharmacokinetic characteristics and possible interactions.

Rapid screening of hepatotoxic components in Uncariae Ramulus Cum Uncis based on "component-target-pathway" network.

As a multi-base source traditional Chinese medicine, the hepatotoxicity of Uncariae Ramulus Cum Uncis (URCU) has been reported repeatedly in recent years. The lack of clarity of toxic components and toxicity mechanisms is a key issue that needs to be addressed. In this article, a "component-target-pathway" network strategy was established to firstly predicting the hepatotoxic components and the toxicity mechanism of URCU. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) and data post-processing technology were used to classify and identify the main components in Uncaria rhynchophylla (Miq.) Miq. ex Havil. (UR) and Uncaria sinensis (Oliv.) Havil. (US). Then, the potential hepatotoxic components were screened by network pharmacology and molecular docking. As a result, 40 components and 39 ingredients were identified in UR and US, respectively. Cadambine, rhynchophylline, corynoxeine, isocorynoxeine, strictosamide and mitraphylline were screened as the potential hepatotoxic ingredients contained both in UR and US. The network pharmacology showed that the potential hepatotoxic components could affect the IL-17 signaling pathway by regulating related targets such as MAPK1 and MAPK14, which might lead to the occurrence of liver injury. This study not only provided a reasonable strategy for the rapid screening of hepatotoxic components in URCU, but also supplied reference and guidance for the rational clinical application and scientific supervision of URCU.

[Secondary metabolites of endophyte Hypoxylon sp. HD-2014 from Uncaria rhynchophylla].

This study aims to investigate the compounds in the product of rice fermented with endophyte Hypoxylon sp.HD-2014 from Uncaria rhynchophylla.To be specific, normal-phase, MCI, Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC) was used to yield 12 compounds.Through spectral data analysis and comparison with previous reports, they were identified as methyl(E)-5-hydroxymethyl-6,7-dihydroxy-4,5-epoxy-octanoate-2-ene(1),(2E,6E)-nona-2,6,8-triene-4,5-diol(2), 8-O-(R)-methoxynodulisporin A(3), 3-nitropropionic acid(4), 3-nitropropionic acid methyl ester(5), 3,4-dihydroxy-phenylethanol(6), 2,4-dichlorobenzoic acid(7), cis-4-hydroxyscytalone(8), 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one(9), isosclerone(10), 4H-1-benzopyran-4-one-2,3-dihydro-5-hydroxy-8-(hydroxyl-methyl)-2-methy(11), and 5-methylmellein(12), respectively.Compounds 1 and 2 were identified for the first time.In vitro cytotoxicity test indicated that compounds 1-12 had no significant inhibitory effect on A549 and HepG2 cells.Antimicrobial susceptibility testing revealed that compound 3 showed synergistic effect with the positive control chloramphenicol.

Biotransformation and pharmacokinetic studies of four alkaloids from Uncaria rhynchophylla in rat plasma by ultra-performance liquid chromatography with tandem mass spectrometry.

Uncaria rhynchophylla (Miq.) Miq. ex Havil (U. rhynchophylla), a traditional Chinese medicine that has been officially included in the Chinese Pharmacopeia, is used to treat cardiovascular and central nervous system diseases. The major alkaloids isolated from U. rhynchophylla are two pairs of epimer including rhynchophylline (RIN) and isorhynchophylline (IRN), along with corynoxeine (CN) and isocorynoxeine (ICN). An ultra-performance liquid chromatography with tandem mass spectrometry method (UHPLC-MS/MS), which was highly accurate, stable and sensitive, was established and validated for the simultaneous determination of four alkaloid compounds (RIN, IRN, CN, ICN) in rat plasma samples after oral administration of RIN, IRN, CN, ICN and U. rhynchophylla extract. In this study, the biotransformation and pharmacokinetics of RIN, IRN, CN and ICN were determined for the first time. An ACQUITY UPLC®HSS T3 column (1.8 µm, 2.1 mm × 100 mm) was used to complete the chromatographic separation within 3 min. The isocratic mobile phase was composed of 0.1 % formic acid water (v/v) and acetonitrile, and the flow rate was 0.2 mL/min. The multireaction monitoring mode was adopted, and the tandem mass spectrometry in the positive ion mode was detected by the electrospray ionization source. The method was fully verified and linear at a wide concentration (r > 0.9913), and the linear concentration range was 0.1552-124.5 ng/mL. The intraday and interday precisions of the four analytes were lower than 8.20 % and 13.42 %, respectively. The accuracy range was - 2.64 % and 13.63 %. The extraction recoveries of the analytes exceeded 83.74 %, and the matrix effect range was 98.43-103.7 % in the plasma samples. The four alkaloids can be quickly absorbed into the blood (Tmax, 0.22-3.83 h) and cleared comparatively slowly (T1/2, 7.67-12.13 h). This method has been successfully applied to the biotransformation and pharmacokinetic studies of SD rat plasma after oral administration of U. rhynchophylla extracts. This proved that RIN with IRN and CN with ICN can transform into each other in vivo. The results are of great significance for determining the mechanism of action and guiding the clinical application of U. rhynchophylla extracts.

Quantitative imaging of natural products in fine brain regions using desorption electrospray ionization mass spectrometry imaging (DESI-MSI): Uncaria alkaloids as a case study.

Uncaria species (Rubiaceae) are used as traditional Chinese medicines (TCMs) to treat central nervous system (CNS) diseases, and monoterpene indole alkaloids are the main bioactive constituents. Localization and quantification of CNS drugs in fine brain regions are important to provide insights into their pharmacodynamics, for which quantitative mass spectrometry imaging (MSI) has emerged as a powerful technique. A systematic study of the quantitative imaging of seven Uncaria alkaloids in rat brains using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was presented. The distribution of the alkaloids in thirteen brain regions was quantified successfully using the calibration curves generated by a modified on-tissue approach. The distribution trend of different Uncaria alkaloids in the rat brain was listed as monoterpene indole alkaloids > monoterpene oxindole alkaloids, R-configuration epimers > S-configuration epimers. Particularly, Uncaria alkaloids were detected directly in the pineal gland for the first time and their enrichment phenomenon in this region had an instructive significance in future pharmacodynamic studies.

Minor monoterpene derivatives from an aqueous extract of the hook-bearing stem of Uncaria rhynchophylla.

Seven new minor monoterpene derivatives (1-7), together with six known analogues, were isolated from an aqueous decoction of the hook-bearing stems of Uncaria rhynchophylla (Gou-teng). Their structures were determined by spectroscopic data analysis and electronic circular dichroism (ECD) calculations, of which 1 was confirmed by single crystal X-ray diffraction.

Transcriptome revealing the dual regulatory mechanism of ethylene on the rhynchophylline and isorhynchophylline in Uncaria rhynchophylla.

Rhynchophylline (RIN) and isorhynchophylline (IRN) are extracted from Uncaria rhynchophylla, which are used to treat Alzheimer's disease. However, the massive accumulation of RIN and IRN in U. rhynchophylla requires exogenous stimulation. Ethylene is a potential stimulant for RIN and IRN biosynthesis, but there is no study on the role of ethylene in RIN or IRN synthesis. This study investigated the regulation of ethylene in RIN and IRN biosynthesis in U. rhynchophylla. An increase in the content of RIN and IRN was observed that could be attributed to the release of ethylene from 18 mM ethephon, while ethylene released from 36 mM ethephon reduced the content of RIN and IRN. The transcriptome and weighted gene co-expression network analysis indicated the up-regulation of seven key enzyme genes related to the RIN/IRN biosynthesis pathway and starch/sucrose metabolism pathway favored RIN/IRN synthesis. In comparison, the down-regulation of these seven key enzyme genes contributed to the reduction of RIN/IRN. Moreover, the inhibition of photosynthesis is associated with a reduction in RIN/IRN. Photosynthesis was restrained owing to the down-regulation of Lhcb1 and Lhcb6 after 36 mM ethephon treatment and further prevented supply of primary metabolites (such as α-D-glucose) for RIN/IRN synthesis. However, uninterrupted photosynthesis ensured a normal supply of primary metabolites at 18 mM ethephon treatment. AP2/ERF1, bHLH1, and bHLH2 may positively regulate the RIN/IRN accumulation, while NAC1 may play a negative regulatory role. Our results construct the potential bidirectional model for ethylene regulation on RIN/IRN synthesis and provide novel insight into the ethylene-mediated regulation of the metabolism of terpenoid indole alkaloids.

Isorhynchophylline ameliorates the progression of osteoarthritis by inhibiting the NF-κB pathway.

Osteoarthritis (OA), a progressive and degenerative joint disease, is characterized by cartilage degradation, synovitis, subchondral bone remodeling and osteophyte formation. Isorhynchophylline (IRN) is an oxindole alkaloid isolated from the traditional Chinese herb Uncaria rhynchophylla. In this study, we evaluated the protective effects of IRN on human OA chondrocytes. IRN treatment dose-dependently decreased the interleukin-1ß (IL-1ß)-induced expressions of nitric oxide (NO; p < 0.001), prostaglandin E2 (PGE2; p < 0.001), tumor necrosis factor alpha (TNF-α; p < 0.001), interleukin-6 (IL-6; p < 0.001), cyclooxygenase-2 (COX-2; p < 0.001) and inducible nitric oxide synthase (iNOS; p < 0.001) in chondrocytes. Meanwhile, the production of metalloproteinase 13 (MMP13; p < 0.001) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5; p < 0.001) was inhibited by IRN treatment. Molecular docking studies revealed that IRN directly interacted with the nuclear factor kappa B (NF-κB) complex, which was associated with a reduced level of NF-κB nuclear translocation and the inhibition of NF-κB signaling activity. Furthermore, administration of IRN generated marked in vivo protective effects during OA development. Collectively, our results demonstrate that IRN may exhibit therapeutic benefits against OA, potentially by ameliorating the inflammative and degenerative progression of OA via inhibiting the NF-κB pathway.

Bioactivity-Guided Separation of Anti-Cholinesterase Alkaloids from Uncaria rhynchophlly (Miq.) Miq. Ex Havil Based on HSCCC Coupled with Molecular Docking.

As an important source of cholinesterase inhibitors, alkaloids in natural products have high potential value in terms of exerting pharmacological activities. In this study, a strategy for targeted preparation of cholinesterase inhibitors in Uncaria rhynchophlly (Miq.) Miq. ex Havil (UR) by high-speed counter-current chromatography was provided. In the method, a two-phase polar solvent system composed of ethyl acetate/n-butanol/water (1:4:5, v/v/v) was used, which isolated five alkaloids from the UR extract for the first time. All alkaloids were identified by HR-ESI-MS and NMR as 7-epi-javaniside (1), vincosamide (2), strictosamide (3), cadambine (4), and 3α-dihydrocadambine (5). The poorly resolved compounds 2 and 3 were separated by preparative HPLC (prep-HPLC). Among them, compounds 1, 4, and 5 were firstly obtained from UR. The purity of these plant isolates was 98.8%, 98.7%, 99.2%, 95.7%, and 98.5%, respectively. Compounds 1-5 exhibited an inhibitory effect on acetyl-cholinesterase and butyryl-cholinesterase with an IC50 from 1.47 to 23.24 µg/mL and 1.01 to 18.24 µg/mL. Molecular docking and inhibitory activities indicated that compound 1 showed stronger inhibitory activity on acetyl-cholinesterase and butyryl-cholinesterase.

Highly antimicrobial and strong cellulose-based biocomposite film prepared with bacterial cellulose powders, Uncaria gambir, and ultrasonication treatment.

This work characterized bacterial cellulose (BC)/Uncaria gambir (G) biocomposite film prepared with ultrasonication treatment. Films were prepared from BC powder suspensions in distilled water without and with various loadings (0.05 g, 0.1 g, 0.2 g, 2 g) of G powder then treated using an ultrasonic probe at 1000 W for one hour. The results revealed that the ultrasonication treatment of the suspension greatly increased tensile strength (TS), elongation at break (EB), and toughness (TN) of a BC film by 3097%, 644%, and 32,600%, respectively, compared to non-sonicated BC film. After adding 0.05 g G into the sonicated BC powder suspension, TS, EB, and TN of the biocomposite film were improved to 105.6 MPa, 14.3%, and 8.7 MJ/m3, respectively. The addition of the G increased in antimicrobial activity of the film. This study indicates that biocomposite film is potentially useful for nanopaper production with good antimicrobial and high tensile properties.

[Steroids from Uncaria rhynchophylla].

Thirteen steroids(1-13) were isolated from the non-alkaloid constituents of Uncaria rhynchophylla by column chromatography on silica gel, ODS, Sephadex LH-20, and preparative HPLC chromatography, and their structures were elucidated by analyses of the MS and NMR spectral data. All the compounds were isolated from the genus Uncaria for the first time, and 1 was a new compound. The ~1H-NMR and ~(13)C-NMR data of two compounds(12 and 13) in deuteron-chloroform were completely assigned. This study enriched the steroid constituents of U. rhynchophylla and provided scientific references for the elucidation of active constituents and further development and utilization of U. rhynchophylla.

Uncaria Rhynchophylla attenuates angiotensin â ¡-induced myocardial fibrosis via suppression of the RhoA/ROCK1 pathway.

Uncaria rhynchophylla (UR), a traditional Chinese medicine, has been proven effective in treating hypertensive patients in China. However, the mechanisms of action of UR in reducing hypertension and myocardial fibrosis are still unclear. The purpose of this study was to explore the role of UR in an angiotensin Ⅱ (Ang Ⅱ) induced mouse model. The mice were randomly divided into 5 groups and infused with Ang Ⅱ (500 ng/kg/min) or saline, then administered UR (0.78, 1.56 or 3.12 g/kg/d) or saline for 4 weeks. UR treatment significantly attenuated the elevation of blood pressure caused by Ang Ⅱ. It enhanced myocardial function and attenuated the increase in the heart weight index and the pathological changes in the Ang Ⅱ-induced hypertensive mice. Furthermore, UR treatment inhibited cardiac fibrosis and significantly down-regulated collagen I, collagen Ⅲ, and α-SMA protein expression in cardiac tissues. UR also attenuated the expression of RhoA, ROCK1, CTGF, and TGF-ß1. In cultured cardiac fibroblasts stimulated with Ang Ⅱ, UR significantly down-regulated the expression of Collagen I, Collagen III, RhoA, ROCK1, and α-SMA. In summary, UR can significantly attenuate Ang Ⅱ-induced hypertension and cardiac fibrosis, partly via suppression of the RhoA/ROCK1 signaling pathway.

Hirsutine ameliorates hepatic and cardiac insulin resistance in high-fat diet-induced diabetic mice and in vitro models.

Closely associated with type 2 diabetes mellitus (T2DM), hepatic steatosis and cardiac hypertrophy resulting from chronic excess intake can exacerbate insulin resistance (IR). The current study aims to investigate the pharmacological effects of hirsutine, one indole alkaloid isolated from Uncaria rhynchophylla, on improving hepatic and cardiac IR, and elucidate the underlying mechanism. T2DM and IR in vivo were established by high-fat diet (HFD) feeding for 3 months in C57BL/6 J mice. In vitro IR models were induced by high-glucose and high-insulin (HGHI) incubation in HepG2 and H9c2 cells. Hirsutine administration for 8 weeks improved HFD-induced peripheral hyperglycemia, glucose tolerance and IR by OGTT and ITT assays, and simultaneously attenuated hepatic steatosis and cardiac hypertrophy by pathological observation. The impaired p-Akt expression was activated by hirsutine in liver and heart tissues of HFD mice, and also in the models in vitro. Hirsutine exhibited the effects on enhancing glucose consumption and uptake in IR cell models via activating phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which was blocked by PI3K inhibitor LY294002. Moreover, the effect of hirsutine on promoting glucose uptake and GLUT4 expression in HGHI H9c2 cells was also prevented by Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Enhancement of glycolysis might be another factor of hirsutine showing its effects on glycemic control. Collectively, it was uncovered that hirsutine might exert beneficial effects on regulating glucose homeostasis, thus improving hepatic and cardiac IR, and could be a promising compound for treating diet-induced T2DM.