Research progress in the study of Clinacanthus nutans and treatment of liver diseases

Background:Based on the long history of medicinal value and modern pharmacological research,a systematic collation of the Clinacanthus nutans has been carried out with a view to providing useful references for the clinical application of the Clinacanthus nutans in hepatoprotection and the research and development of new drugs.Methods:The research progress of a large number of domestic and international studies on the therapeutic mechanism of the antiliver diseases of Clinacanthus nutans and its active ingredients is summarized.The aim is to explore the greater value of the herb.Results:The major chemical constituents with pharmacological activities of the Clinacanthus nutans were summarized,and a feasible mechanism of action was compiled and analyzed.Conclusion:Many studies have confirmed the great medicinal value of Clinacanthus nutans and its active monomer components,especially in the prevention and treatment of liver diseases,which is worthy of more in-depth research,development and utilization.Chinese medicine is the treasure of China,therefore,it should be used in more clinical applications.

Clinacanthus nutans:a review of the medicinal uses,pharmacology and phytochemistry

Clinacanthus nutans Lindau is known as snake grass belonging to the Acanlhaceae family.This plant has diverse and potential medicinal uses in traditional herbal medicine for treating skin rashes,insects and snake bites,lesions caused by herpes simplex virus,diabetes,and gout in Malaysia.Indonesia.Thailand and China.Phylochemieal investigations documented the varied contents of bioaclive compounds from litis plant namely flavonoids,glycosides,glycoglyeerolipids.cerebrosides and monoacylmonogalatosylglycerol.The pharmacological experiment proved that various types of extracts and pure compounds from this species exhibited a broad range of biological properties such as anti-inflammatory,antiviral,antioxidant,and anti-diabetic activities.The lindings of toxicity study showed that extracts from this plant did not show any toxicity thus it can be used as strong therapeutic agents for specific diseased conditions.However,further experiments on chemical components and their mode of action showing biological activities are required to elucidate the complete phytochemical profile and assess to confirm their suitability tor future drugs.This review summarizes the medicinal uses,phytochemistry and pharmacology of this plant in order to explore its therapeutic potential and gaps necessitating for prospected research work.

The identities and anti-herpes simplex virus activity of Clinacanthus nutans and Clinacanthus siamensis

Objective:To distinguish the difference among the Clinacanthus nutans(Burm.f.)Lindau(C.nutans)and Clinacanthus siamensis Bremek(C.siamensis)by assessing pharmacognosy characteristics,molecular aspect and also to evaluate their anti-herpes simplex virus(HSV)type 1 and type 2 activities.Methods:Macroscopic and microscopic evaluation were performed according to WHO Geneva guideline.Stomatal number,stomatal index and palisade ratio of leaves were evaluated.Genomic DNA was extracted by modified CTAB method and ITS region was amplified using PGR and then sequenced.Dry leaves were subsequently extracted with n-hexane,dichloromethane and methanol and antiviral activity was performed using plaque reduction assay and the cytotoxicity of the extracts on Vero cells was determined by MTT assay.Results:Cross section of midrib and stem showed similar major components.Leaf measurement index of stomatal number,stomatal index and palisade ratio of C.nutans were 168.32±29.49,13.83±0.86 and 6.84±0.66,respectively,while C.siamensis were 161.60±18.04,11.93±0.81and 3.37±0.31,respectively.The PCR amplification of ITS region generated the PGR product approximately 700 bp in size.There were 34 polymorphisms within the ITS region which consisted of 11 Indels and 23 nucleotide substitutions.The IC_(50)values of C.nutans extracted with n-hexane,dichloromethane and methanol against HSV-1 were(32.05±3.63)μg/mL,(44.50±2.66)μg/mL,(64.93±7.00)μg/mL,respectively where as those of C.siamensis were(60.00±11.61)μg/mL,(55.69+4.41)μg/mL,(37.39±5.85)μg/mL,respectively.Anti HSV-2 activity of n-hexane,dichloromethane and methanol C.nutans leaves extracts were(72.62±12.60)μg/mL,(65.19±21.45)μg/mL,(65.13±2.22)μg/mL,respectively where as those of C.siamensis were(46.52±4.08)μg/mL,(49.63±2.59)μg/mL,(72.64±6.52)μg/mL,respectively.Conclusions:The combination of macroscopic,microscopic and biomolecular method are able to authenticate these closely related plants and both of them have a potency to be an anti-HSV agent.

Anti-herpes simplex virus activities of monogalactosyl diglyceride and digalactosyl diglyceride from Clinacanthus nutans, a traditional Thai herbal medicine

Objective: To evaluate the monogalactosyl diglyceride(MGDG) and digalactosyl diglyceride(DGDG) from Clinacanthus nutans(C. nutans) for their in vitro antiviral activities against herpes simplex virus type 1(HSV-1) and type 2(HSV-2) by plaque reduction assay.Methods: MGDG and DGDG were extracted with chloroform from C. nutans leaves.MGDG and DGDG were separated from chloroform crude extract using column chromatography, characterized by thin layer chromatography and quantified by high performance liquid chromatography. The anti HSV-1 and 2 activity against pre-treatment and posttreatment of the compounds was evaluated using plaque reduction assay. The cytotoxicity of the extract and the compounds on Vero cells were performed by MTT assay.Results: MGDG and DGDG obtained by column chromatography showed identical profiles as standard MGDG and standard DGDG using thin layer chromatography and high performance liquid chromatography. MGDG and DGDG from C. nutans showed 100%inhibition of HSV-1 replication at the post step of infection at noncytotoxic concentration with IC50 values of 36.00 and 40.00 mg/m L, and HSV-2 at 41.00 and 43.20 mg/mL,respectively. Moreover, MGDG and DGDG from C. nutans were demonstrated to have antiherpes simplex activity at the same level as standard synthetic compounds. In contrast, pretreatment of Vero cells with MGDG and DGDG before HSV-1 and HSV-2 infection did not show inhibitory effect against these viruses. MGDG and DGDG exhibited antiviral activity against HSV-1 with selectivity index of 26.00 and 23.00 and HSV-2 of 23.30 and 21.30.Conclusions: MGDG and DGDG from C. nutans, a traditional Thai herbal medicine illustrated inhibitory activity against HSV-1 and HSV-2, probably by inhibiting the late stage of multiplication, suggesting their promising use as anti-HSV agents.

Identification of α-glucosidase inhibitors from Clinacanthus nutans leaf extract using liquid chromatography-mass spectrometry-based metabolomics and protein-ligand interaction with molecular docking

The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. nHexane, n-hexane: ethyl acetate(1:1, v/v), ethyl acetate, ethyl acetate: methanol(1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square(PLS) statistical model was developed using the SIMCA P^+14.0 software and the following four inhibitors were obtained:(1) 4,6,8-Megastigmatrien-3-one;(2) N-Isobutyl-2-nonen-6,8-diynamide;(3) 1′,2′-bis(acetyloxy)-3′,4′-didehydro-2′-hydro-β, ψ-carotene; and(4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase(PDB code: 3 A4 A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335,and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313,VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.

Effects of Ethanol Extract of Clinacanthus nutans on Gut Microbiota and Lipid Metabolism of HFD-induced Obese Mice

[Objectives]To explore the effects of ethanol extract of Clinacanthus nutans on gut microbiota and lipid metabolism in high-fat diet(HFD)-induced obese mice.[Methods]A HFD-induced obesity mouse model was established,and the mice were randomly divided into high-fat model group,high-dose and low-dose groups of ethanol extract of C.nutans.Normal group and high-fat model group were given normal saline by intragastric administration every day.The high-dose and low-dose groups of the ethanol extract of C.nutans were given corresponding drugs by intragastric administration.After 8 weeks of administration,the body weight,fat accumulation,blood lipid level,and liver histopathological changes of the mice in each group were compared.The high-throughput sequencing of 16S rRNA was used to sequence the fecal samples of mice in each group,and the effects of ethanol extract of C.nutans on lipid metabolism and gut microbiota structure in HFD-induced obese mice were analyzed.[Results]Compared with the normal group,the high-fat model group had significantly higher body weight(P<0.01),increased subcutaneous fat accumulation(P<0.01),increased liver fat content,and increased serum TC,TG and LDL levels(P<0.01).Compared with the high-fat model group,the high-dose group of the ethanol extract of C.nutans significantly reduced the body weight of obese mice(P<0.01),reduced the subcutaneous fat accumulation in obese mice(P<0.05),inhibited the synthesis of fat in the liver,significantly reduced serum TC,TG levels(P<0.01),and significantly increased serum HDL levels(P<0.01).Compared with the normal group,the relative abundance of Firmicutes and Proteobacteria in the gut microbiota of mice in the high-fat model group was significantly increased,while the relative abundances of Bacteroidetes,Verrucomicrobia,and Akkermansia were significantly decreased(P<0.01),and the ratio of Firmicutes to Bacteroidetes was significantly increased.After treatment with ethanol extract of C.nutans,the ratio of Firmicutes to Bacteroidetes was reduced,the relative abundance of Bacteroidetes,Verrucomicrobia and Akkermansia(AKK)increased(P<0.05),while the relative abundance of Firmicutes and Proteobacteria decreased(P<0.05).[Conclusions]HFD-induced obese mice have imbalanced gut microbiota structure and abnormal lipid metabolism,and the ethanol extract of C.nutans can improve the imbalance of microbiota structure and lipid metabolism in obese mice.

Geographical Traceability of Clinacanthus nutans with Near-Infrared Pectroscopy and Chemometrics

In this study, a seed origin discrimination model for Clinacanthus nutans was developed. First, 81 C. nutans samples from three seed origin locations were collected, and their Near-Infrared (NIR) spectra were obtained. Next, Principal Component Analysis (PCA) was performed on the NIR spectra of the 81 C. nutans samples. Then, MSC (multiplicative scatter correction), SNV (standard normal variate), first derivative, and second derivative pre-treatments of the C. nutans spectra were performed and combined with the Support Vector Machine (SVM) algorithm for modelling and analysis. Among these methods, first-order derivative pre-treatment achieved the best SVM model effectiveness, with a training set accuracy of 93.44% (57/61) and a test set accuracy of 85.00% (17/20). In order to further improve the discrimination accuracy of the model, three optimization algorithms Grid Search (GS), Genetic Algorithm (GA), and Particle Swarm Optimization (PSO) were employed to identify the best c and g parameters for the SVM model. The results demonstrated that the PSO optimization algorithm yielded the best parameters of c = 0.8343, g = 57.8741, with corresponding model training set the accuracy of 96.36% (60/61) and test set the accuracy of 95.00% (20/21). Therefore, developing a seed origin classification model for C. nutans based on NIR spectroscopy combined with chemometrics is feasible and has the advantages of being simple, rapid, and green.

忧遁草抗氧化活性评价和总黄酮、总多酚含量测定

忧遁草富含黄酮类、多酚类、甾醇类、三萜类、生物碱类和糖苷类等化合物,具有清热解毒、利尿消肿和祛湿等功效。为了进一步探究忧遁草的有效活性部位,本研究对其根、茎、叶三个部位进行了清除ABTS和DPPH自由基的能力测定,建立TBHP诱导HepG2细胞氧化损伤模型,采用三氯化铝和福林酚比色法测定忧遁草不同部位的粗提物中总黄酮和总多酚的含量。结果表明,忧遁草对ABTS和DPPH自由基有一定的清除作用,根、茎、叶提取物对清除ABTS和DPPH自由基的IC50分别为:(0.68±0.074)mg/mL、(1.34±0.108)mg/mL、(0.41±0.006)mg/mL和(0.46±0.013)mg/mL、(0.644±0.016)mg/mL、(0.408±0.018)mg/mL,其作用效果叶>根>茎。忧遁草根、茎、叶提取物对HepG2细胞的氧化损伤也有一定的保护作用,且作用效果均为叶>根>茎,叶片提取物浓度为10μg/mL时,可将细胞存活率由(45.18±2.429)%提高至(78.07±3.188)%。忧遁草不同部位的总黄酮和总多酚含量分别在(3.01±0.055)%^(5.43±0.072)%和(0.74±0.043)%^(1.42±0.124)%之间,其中叶片中黄酮和多酚含量最高。忧遁草的抗氧化活性和总黄酮、多酚含量存在相关性。忧遁草提取物具有良好的抗氧化效果,尤其是叶提取物,具有较高的开发利用价值,有望开发成为新型食品添加剂或抗氧化剂。