The basic chemical substances of total alkaloids of Uncaria rhynchophylla and their anti-neuroinflammatory activities.

To clarify the chemical basis of the total alkaloids of Uncaria rhynchophylla, HPLC-VWD chromatogram of total alkaloids was established. Under its guidance, modern chromatographic and spectroscopic techniques were used to track, isolate and identify the representative principal components. As a result, one new monoterpenoid indole alkaloid, 3S,15S-N4-methoxymethyl-geissoschizine methyl ether (1), together with 20 known alkaloids (2-21), and 5 other known compounds (22-26) were obtained. Meanwhile, sixteen characteristic peaks were identified from the total alkaloids using HPLC analysis. Then, the anti-neuroinflammatory effect of compounds 1-21 was assessed through inhibiting nitric ---oxide (NO) production in lipopolysaccharide (LPS)-induced BV-2 microglial cells. Among them, compounds 1, 3, 7, 8, 11, 12, 19 and 21 showed potent inhibitory activities with IC50 values of 5.87-76.78 µM.

Effect of nitrogen reduction by chemical fertilization with green manure (Vicia sativa L.) on soil microbial community, nitrogen metabolism and and yield of Uncaria rhynchophylla by metagenomics.

Uncaria rhynchophylla is an important herbal medicine, and the predominant issues affecting its cultivation include a single method of fertilizer application and inappropriate chemical fertilizer application. To reduce the use of inorganic nitrogen fertilization and increase the yield of Uncaria rhynchophylla, field experiments in 2020-2021 were conducted. The experimental treatments included the following categories: S1, no fertilization; S2, application of chemical NPK fertilizer; and S3-S6, application of chemical fertilizers and green manures, featuring nitrogen fertilizers reductions of 0%, 15%, 30%, and 45%, respectively. The results showed that a moderate application of nitrogen fertilizer when combined with green manure, can help alleviate soil acidification and increase urease activity. Specifically, the treatment with green manure provided in a 14.71-66.67% increase in urease activity compared to S2. Metagenomics sequencing results showed a decrease in diversity in S3, S4, S5, and S6 compared to S2, but the application of chemical fertilizer with green manure promoted an increase in the relative abundance of Acidobacteria and Chloroflexi. In addition, the nitrification pathway displayed a progressive augmentation in tandem with the reduction in nitrogen fertilizer and application of green manure, reaching its zenith at S5. Conversely, other nitrogen metabolism pathways showed a decline in correlation with diminishing nitrogen fertilizer dosages. The rest of the treatments showed an increase in yield in comparison to S1, S5 showing significant differences (p < 0.05). In summary, although S2 demonstrate the ability to enhance soil microbial diversity, it is important to consider the long-term ecological impacts, and S5 may be a better choice.

Genome-wide identification of GATA transcription factor family and the effect of different light quality on the accumulation of terpenoid indole alkaloids in Uncaria rhynchophylla.

Uncaria rhynchophylla is an evergreen vine plant, belonging to the Rubiaceae family, that is rich in terpenoid indole alkaloids (TIAs) that have therapeutic effects on hypertension and Alzheimer's disease. GATA transcription factors (TF) are a class of transcription regulators that participate in the light response regulation, chlorophyll synthesis, and metabolism, with the capability to bind to GATA cis-acting elements in the promoter region of target genes. Currently the charactertics of GATA TFs in U. rhynchophylla and how different light qualities affect the expression of GATA and key enzyme genes, thereby affecting the changes in U. rhynchophylla alkaloids have not been investigated. In this study, 25 UrGATA genes belonging to four subgroups were identified based on genome-wide analysis. Intraspecific collinearity analysis revealed that only segmental duplications were identified among the UrGATA gene family. Collinearity analysis of GATA genes between U. rhynchophylla and four representative plant species, Arabidopsis thaliana, Oryza sativa, Coffea Canephora, and Catharanthus roseus was also performed. U. rhynchophylla seedlings grown in either red lights or under reduced light intensity had altered TIAs content after 21 days. Gene expression analysis reveal a complex pattern of expression from the 25 UrGATA genes as well as a number of key TIA enzyme genes. UrGATA7 and UrGATA8 were found to have similar expression profiles to key enzyme TIA genes in response to altered light treatments, implying that they may be involved in the regulation TIA content. In this research, we comprehensively analyzed the UrGATA TFs, and offered insight into the involvement of UrGATA TFs from U. rhynchophylla in TIAs biosynthesis.

Triterpenoids from the hook-bearing stems of Uncaria rhynchophylla.

An unprescribed nortriterpenoid with an aromatic E ring, uncanortriterpenoid A (1), together with fourteen known triterpenoids (2-15), were isolated from the hook-bearing stems of Uncaria rhynchophylla Miq. Based on extensive spectroscopic analyses, the NMR data of 2, 5, and 10 in CD3OD were assigned for the first time, and the wrongly assigned δC of C-27 and C-29 of 2 were revised. Among the known compounds, 7, 13, and 15 were isolated from this species for the first time, and 15 represents the first lanostane triterpenoid bearing an extra methylidene at C-24 for the Rubiaceae family. Additionally, compounds 6 and 14 exhibited moderate ferroptosis inhibitory activity, with an EC50 value of 14.74 ± 0.20 µM for 6 and 23.11 ± 1.31 µM for 14.

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

Seven new monoterpene alkaloids (1 - 7), along with 16 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, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 1 and 2 are stereoisomers belonging to a novel type of pseudoindoxyl monoterpene alkaloids, 3 is the first monoterpene furoindole alkaloid from nature, and 4 - 7 are derivatives of the known monoterpene alkaloids featuring different structures.

Metabolite profiling and identification of enzymes responsible for the metabolism of hirsutine, a major alkaloid from Uncaria rhynchophylla.

The in vitro metabolism of hirsutine was determined using liver microsomes and human recombinant cytochrome P450 enzymes. Under the current conditions, a total of 14 phase I metabolites were tentatively identified.Ketoconazole showed significant inhibitory effect on the metabolism of hirsutine. Human recombinant cytochrome P450 enzyme analysis revealed that metabolism of hirsutine was mainly catalysed by CYP3A4.Our data revealed that hirsutine was metabolised via mono-oxygenation, di-oxygenation, N-oxygenation, dehydrogenation, demethylation and hydrolysis.In glutathione (GSH)-supplemented liver microsomes, four GSH adducts were identified. Hirsutine underwent facile P450-mediated metabolic activation, forming reactive 3-methyleneindolenine and iminoquinone intermediates.This study provided valuable information on the metabolic fates of hirsutine in liver microsomes, which would aid in understanding the hepatotoxicity caused by hirsutine or hirsutine-containing herb preparation.

Discovery and Biomimetic Semisynthesis of Spirophyllines A-D from Uncaria rhynchophylla.

Spirophyllines A-D (1-4), four new spirooxindole alkaloids all characterized by the spiro[pyrrolidin-3,3'-oxindole] core and a rare isoxazolidine ring, were isolated from Uncaria rhynchophylla. Their structures were determined by spectroscopic methods and confirmed by X-ray crystallography. Based on the biomimetic semisynthesis strategy, compounds 1-8 were synthesized in three steps via the key reactions of 1,3-dipolar cycloaddition and Krapcho decarboxylation from corynoxeine. Interestingly, compound 3 showed moderate inhibitory activity against the Kv1.5 potassium channel (IC50 = 9.1 µM).

Chloroplast genome characterization of Uncaria guianensis and Uncaria tomentosa and evolutive dynamics of the Cinchonoideae subfamily.

Uncaria species are used in traditional medicine and are considered of high therapeutic value and economic importance. This work describes the assembly and annotation of the chloroplast genomes of U. guianensis and U. tomentosa, as well as a comparative analysis. The genomes were sequenced on MiSeq Illumina, assembled with NovoPlasty, and annotated using CHLOROBOX GeSeq. Addictionaly, comparative analysis were performed with six species from NCBI databases and primers were designed in Primer3 for hypervariable regions based on the consensus sequence of 16 species of the Rubiaceae family and validated on an in-silico PCR in OpenPrimeR. The genome size of U. guianensis and U. tomentosa was 155,505 bp and 156,390 bp, respectively. Both Species have 131 genes and GC content of 37.50%. The regions rpl32-ccsA, ycf1, and ndhF-ccsA showed the three highest values of nucleotide diversity within the species of the Rubiaceae family and within the Uncaria genus, these regions were trnH-psbA, psbM-trnY, and rps16-psbK. Our results indicates that the primer of the region ndhA had an amplification success for all species tested and can be promising for usage in the Rubiaceae family. The phylogenetic analysis recovered a congruent topology to APG IV. The gene content and the chloroplast genome structure of the analyzed species are conserved and most of the genes are under negative selection. We provide the cpDNA of Neotropical Uncaria species, an important genomic resource for evolutionary studies of the group.

Study on material basis and anti-hypertensive metabolomics of different extraction methods of the Uncaria rhynchophylla Scrophularia Formula.

Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Uncaria rhynchophylla Scrophularia Formula (URSF), a medical institution preparation of the affiliated Hospital of Shandong University of Traditional Chinese Medicine, is effective for essential hypertension. However, the efficacy of URSF for hypertension remains unclear. We aimed to clarify the anti-hypertensive mechanism of the URSF. The material basis of URSF was identified by the LC-MS. We also evaluated the antihypertensive efficacy of URSF on SHR rats by body weight, blood pressure and biochemical indicators. The LC-MS spectrometry-based serum non-targeted metabolomics was used to seek potential biomarkers and relevant pathways for URSF in the treatment of SHR rats. 56 biomarkers were metabolically disturbed in SHR rats in the model group compared with the control group. After URSF intervention, 13 biomarkers showed a recovery in the optimal method compared with the other three groups. We identified 3 metabolic pathways in which URSF is involved: the arachidonic acid metabolism pathway, the niacin and nicotinamide metabolism pathway, and the purine metabolism pathway. These discoveries offer a basis for the study of URSF for the treatment of hypertension.

Identification of three key enzymes involved in the biosynthesis of tetracyclic oxindole alkaloids in Uncaria rhynchophylla.

Tetracyclic oxindole alkaloids (TOAs), main active ingredients of Uncaria rhynchophylla (UR), has inspired the interest of pharmacologists and chemists because of its great potential in the treatment of the diseases of the nervous system and cardiovascular system and its special spirooxindole scaffold, but the biosynthetic pathway of this compounds is still unknown. In this work, the metabolomics and transcriptomics of hook, leaf and stem of UR were analyzed, and 31 alkaloids and 47,423 unigenes were identified, as well as the relative contents of these alkaloids were evaluated. Based on the above results and literatures, a proposal biosynthetic pathway for TOAs was devised. Furthermore, three unigenes were suggested mediating the biosynthesis of TOAs through the integrated analysis of metabolomics and transcriptomics, and three enzymes, tryptophan decarboxylase, strictosidine synthase and strictosidine-ß-d-glucosidase, were identified as important catalytic enzymes for the synthesis of tryptamine, strictosidine (7) and 4,21-dehydrogeissochizine, respectively, which are considered as the important precursors of TOAs.

Triterpenoids from Uncaria macrophylla as ferroptosis inhibitors.

Seven undescribed triterpenoids were obtained from the ethanol extract of the dried stems of Uncaria macrophylla Wall. (Rubiaceae).All of the isolates were urs-28-oic acid or olean-28-oic acid skeletons, including three triterpenoids with rare 3ß,23-(1R-4-hydroxy-butyl-1,1-dioxy) or 23-(2R-tetrahydrofuran-2-oxy) substituents. Five triterpenoids showed promising inhibitory activity against erastin-induced ferroptosis in PC12 cells, while 3ß,6α,23-trihydroxy-olean-12-en-28-oic acid was the most significant inhibitor to resist ferroptosis by activating the Nrf2/SLC7A11/GPx4 axis with an EC50 value of 4.2 ± 0.7 µM.

Uncariphyllin A-J, indole alkaloids from Uncaria rhynchophylla as antagonists of dopamine D2 and Mu opioid receptors.

Ten new indole alkaloids (1-10) as well as eleven known analogs (11-21) were isolated from the stems and hooks of Uncaria rhynchophylla. Their structure elucidation was based on extensive NMR studies, MS and ECD data, with the essential aid of DFT prediction of ECD spectra. Compound 1 was determined as a 17,19-seco-cadambine-type alkaloid, and compound 3 was confirmed to be a 3,4-seco-tricyclic monoterpene indole alkaloid, which are the first seco-alkaloids possessing such cleavage positions from U. rhynchophylla. All the isolated compounds were evaluated for their bioactivities on dopamine D2 and Mu opioid receptors for discovering natural therapeutic drugs targeting central nervous system (CNS) diseases. Compounds 1, 2, 4, 5, 20 and 21 showed antagonistic bioactivities on the D2 receptor (IC50 0.678-15.200 µM), and compounds 1, 3, 6, 9, 10, 13, 18, 19 and 21 exhibited antagonistic effects on the Mu receptor (IC50 2.243-32.200 µM). Among them, compounds 1 and 21 displayed dual-target activities. Compound 1 showed conspicuous antagonistic activity on D2 and Mu receptors with the IC50 values of 0.678 ± 0.182 µM and 13.520 ± 2.480 µM, respectively. Compound 21 displayed moderate antagonistic activity on the two receptors with the IC50 values at 15.200 ± 1.764 µM and 32.200 ± 5.695 µM, respectively.

A pair of new oxindole alkaloids isolated from Uncaria macrophylla.

A pair of new oxindole alkaloids, named macrophyllines C (1) and D (2), together with two known oxindole alkaloids isorhynchophylline (3) and corynoxine (4) were isolated from Uncaria macrophylla. Their structures were elucidated based on detailed spectroscopic analysis and by comparison with literature data. In addition, all the isolates were tested for their anti-HIV activities and cytotoxicities in C8166 cells and compounds 2-4 showed weak anti-HIV activities with EC50 values of 11.31 ± 3.29 µM, 18.77 ± 6.14 µM and 30.02 ± 3.73 µM, respectively.

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.

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.

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.

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.