Safety Assessment and Hepatic-Renal Protection of Cajanus cajan (L.) Millsp. Root and Its Soy Isoflavone Contents.

Cajanus cajan (L.) Millsp., also known as pigeon pea, has roots that have exhibited much pharmacological potential. The present study was conducted to assess the safe dose of the ethanolic extract of C. cajan roots (EECR95) and to analyze the main soy isoflavones contents. In vitro, we investigated the mutagenicity and cytotoxic effect of EECR95 on Salmonella typhimurium-TA98 and TA100 (by Ames tests) and RAW 264.7, L-929, and HGF-1 cell lines (by MTT tests) for 24 h of incubation. We found no mutagenic or cytotoxic effects of EECR95. After administration of 0.2 or 1.0 g/kg bw of EECR95 to both male and female Wistar rats for 90 days, there were no significant adverse effects on the behaviors (body weight, water intake, and food intake), organ/tissue weights, or immunohistochemical staining, and the urine and hematological examinations of the rats were within normal ranges. EECR95 potentially decreases renal function markers in serum (serum uric acid, BUN, CRE, and GLU) or liver function markers (cholesterol, triglyceride, and glutamic-pyruvate-transaminase (GPT)). We also found that EECR95 contained five soy isoflavones (genistein, biochanin A, daidzein, genistin, and cajanol), which may be related to its hepatorenal protection. Based on the high dose (1.0 g/kg bw) of EECR95, a safe daily intake of EECR95 for human adults is estimated to be 972 mg/60 kg person/day.

Four new stilbenes and one new flavonoid with potential antibacterial and anti-SARS-CoV-2 activity from Cajanus cajan.

Four new stilbenes (1-4) and one new flavonoid (5), named cajanines D-H, together with three known stilbenes (6-8) were isolated from the leaves of Cajanus cajan (L.) Millsp. (pigeon pea). The structures of these compounds were elucidated unambiguously on the basis of IR, 1D, and 2D NMR, as well as HRESIMS data. Structurally, stilbenes 1-4 bore an isopentyl side chain, and further hydroxylation of compounds 1-3 generated a greater variety of structural forms. Compound 5 was a flavonoid owning an isopentyl side chain. Besides, antibacterial activity of the isolated compounds against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was studied in vitro. Compounds 1-8 were endowed with profound antibacterial activity. Among them, the MIC values of compounds 4, 6, and 7 against S. aureus were 1.56, 0.78, and 0.78 µg/mL, respectively, among which 6 and 7 had better antibacterial activity than the positive control Vancomycin with the MIC values of 1.56 µg/mL. Additionally, the anti-SARS-CoV-2 main protease activity of all the isolated compounds was evaluated, and it was worth mentioning that the IC50 values of compounds 5-7 were 8.27, 4.65, and 8.30 µM, respectively, being comparable to the positive control Ebselen. Our findings may provide valuable guidance for the application of stilbenes as lead compounds in the future for the development of drugs with antibacterial or anti-COVID-19 activity.

Stilbenoids and Flavonoids from Cajanus cajan (L.) Millsp. and Their α-Glucosidase Inhibitory Activities.

Two new stilbenoids, cajanstilbenoid C (1) and cajanstilbenoid D (2), together with eight other known stilbenoids (3-10) and seventeen known flavonoids (11-27), were isolated from the petroleum ether and ethyl acetate portions of the 95% ethanol extract of leaves of Cajanus cajan (L.) Millsp. The planar structures of the new compounds were elucidated by NMR and high-resolution mass spectrometry, and their absolute configurations were determined by comparison of their experimental and calculated electronic circular dichroism (ECD) values. All the compounds were assayed for their inhibitory activities against yeast α-glucosidase. The results demonstrated that compounds 3, 8-9, 11, 13, 19-21, and 24-26 had strong inhibitory activities against α-glucosidase, with compound 11 (IC50 = 0.87 ± 0.05 µM) exhibiting the strongest activity. The structure-activity relationships were preliminarily summarized. Moreover, enzyme kinetics showed that compound 8 was a noncompetitive inhibitor, compounds 11, 24-26 were anticompetitive, and compounds 9 and 13 were mixed-competitive.

Molecular mechanism of naringenin regulation on flavonoid biosynthesis to improve the salt tolerance in pigeon pea (Cajanus cajan (Linn.) Millsp.).

Flavonoids are important secondary metabolites in the plant growth and development process. As a medicinal plant, pigeon pea is rich in secondary metabolites. As a flavonoid, there are few studies on the regulation mechanism of naringenin in plant stress resistance. In our study, we found that naringenin can increase the pigeon pea's ability to tolerate salt and influence the changes that occur in flavonoids including naringenin, genistein and biochanin A. We analyzed the transcriptome data after 1 mM naringenin treatment, and identified a total of 13083 differentially expressed genes. By analyzing the metabolic pathways of these differentially expressed genes, we found that these differentially expressed genes were enriched in the metabolic pathways of phenylpropanoid biosynthesis, starch and sucrose metabolism and so on. We focused on the analysis of flavonoid biosynthesis related pathways. Among them, the expression levels of enzyme genes CcIFS, CcCHI and CcCHS in the flavonoid biosynthesis pathway had considerably higher expression levels. By counting the number of transcription factors and the binding sites on the promoter of the enzyme gene, we screened the transcription factors CcMYB62 and CcbHLH35 related to flavonoid metabolism. Among them, CcMYB62 has a higher expression level than the others. The hairy root transgene showed that CcMYB62 could induce the upregulation of CcCHI, and promote the accumulation of naringenin, genistein and biochanin A. Our study revealed the molecular mechanism of naringenin regulating flavonoid biosynthesis under salt stress in pigeon pea, and provided an idea for the role of flavonoids in plant resistance to abiotic stresses.

Revisiting the Nutritional, Chemical and Biological Potential of Cajanus cajan (L.) Millsp.

The genus Cajanus (Family: Fabaceae) consists of approximately 37 species, and Cajanus cajan (C. cajan) is a significant member of the genus. It is a commercial legume crop widely grown in sub-tropical and semi-arid tropical areas of the world. C. cajan is well known for its folk medicinal uses to treat various disorders, such as toothache, dizziness, diabetes, stomachache, female ailments and chronic infections. These properties have been linked to the presence of several value-added nutritional and bioactive components. Different solvent extracts from C.cajan (leaves, root, stem and seeds) have been evaluated for their phytochemical and biological activities, namely antioxidant, antimicrobial, antidiabetic, neuroprotective, and anti-inflammatory effects. Taken together, and considering the prominent nutraceutical and therapeutic properties of C. cajan, this review article focuses on the important details including ethnomedicinal uses, chemical composition, biological applications and some other medicinal aspects related to C.cajan nutraceutical and pharmacological applications.

Stilbenes from the leaves of Cajanus cajan and their in vitro anti-inflammatory activities.

Eighteen stilbenes (1-18), including six previously undescribed ones (1-6), with diverse modification patterns were isolated from the leaves of edible and medicinal plant Cajanus cajan. Among the new isolates, compounds 1-3 were initially obtained as three racemic mixtures, which were further resolved into three pairs of optically pure enantiomers, respectively, by chiral HPLC. Besides, compounds 8, 10, 11, and 18 were obtained from C. cajan for the first time. The chemical structures and absolute configurations of the new stilbenes were elucidated unambiguously on the basis of extensive spectroscopic analyses, single crystal X-ray crystallographic study, and quantum chemical electronic circular dichroism (ECD) calculations. In addition, the in vitro anti-inflammatory activities of all isolated stilbenes were evaluated. Compounds 2, 9, 10, 11, and 14 exerted moderate suppression of nitric oxide (NO) secretion in lipopolysaccharide (LPS)-induced RAW264.7 cells without exhibiting substantial cytotoxicity.

Health-Promoting Phenolic Compound Accumulation, Antioxidant Response, Endogenous Salicylic Acid Generation, and Biosynthesis Gene Expression in Germinated Pigeon Pea Seeds Treated with UV-B Radiation.

Germinated pigeon pea seeds (GPPSs) are good dietary supplements with satisfactory nutritional and medicinal values. In this study, UV-B treatment was used to promote the accumulation of health-promoting phenolic compounds (10 flavonoids and 1 stilbene) in GPPS. The total yield of 11 phenolic compounds (235 839.76 ± 17 118.24 ng/g DW) significantly improved (2.53-fold increase) in GPPSs exposed to UV-B radiation (3 W/m2) for 8 h, whereas free amino acid and reducing sugar contents exhibited a decreasing tendency during UV-B exposure. Meanwhile, the positive response in the antioxidant activities of enzymes and nonenzymatic extracts was noticed in UV-B-treated GPPSs. Moreover, UV-B radiation could cause tissue damages in hypocotyls and cotyledons of the GPPSs and enhance the generation of endogenous salicylic acid, thus activating the expression of biosynthesis genes (especially CHS and STS1). Overall, the simple UV-B supplementation strategy makes GPPSs more attractive as functional foods/nutraceuticals in diet for promoting human health.

The Dietary Use of Pigeon Pea for Human and Animal Diets.

Pigeon pea (PP) [Cajanus cajan (L.) Huth] plays an important role in preserving poor smallholders' major source of income in the tropics and subtropics by improving food and feed security, particularly protein intake. In the meantime, protein deficiency is frequent in tropical and subtropical regions due to rapidly increasing human populations and the high cost of animal-origin proteins. As a result, pulse crops should be their primary source of protein. Among these, PP is the most important pulse crop utilized as a food component in rain-fed agricultural conditions with the lowest costs, and it is the best source of protein supplements in typical cereal-based diets to fill the nutritional deficit. Despite this, it is the world's least-used pulse crop. Therefore, the primary goal of this review was to provide and synthesize scientifically confirmed and up-to-date information on the dietary usage of pigeon pea for food and feed. Protein, carbohydrates, minerals, vitamins, and essential amino acids are all present in reasonable amounts in both mature and immature PP seeds. PP has the most potential for usage as food and feed, and its nutrients are comparable to those of soybeans and maize. PP's green leaves, roots, seeds, and pods are high in phenolic compounds, which have anti-inflammation, antibacterial, antioxidant, anticarcinogenic, and antidiabetic properties, as well as the ability to cure diseases like measles, smallpox, chicken pox, sickle cell anemia, fever, dysentery, hepatitis, and antimalarial medications for the body. Furthermore, the addition of pigeon pea and its by-products improves ruminant and nonruminant animal feeding performance significantly. In general, PP products such as dried grain, fresh (aerial portion), and green pods are used as a low-cost (low-cost) source of high-quality and quantity of protein food and feed for tropical and subtropical populations' livelihoods.

GC-MS and LC-MS: an integrated approach towards the phytochemical evaluation of methanolic extract of Pigeon Pea [Cajanus cajan (L.) Millsp] leaves.

Pigeon Pea is a well-received traditional nutritious and medicinal plant in India since ancient times. The plant is identified for its impressive pharmacological activities like antimicrobial, anti-inflammatory, antitubercular, antioxidant, neuroprotective, antihypertensive, antihyperglycemic and anticancer properties. The metabolites from Pigeon Pea leaves methanolic extract were identified using hyphenated instruments namely Gas Chromatography-Mass Spectroscopy (GC-MS) and Liquid Chromatography-Mass Spectroscopic (LC-MS) method. GC and LC chromatogram showed proper separation and presence of several bioactive compounds such as flavonoids, terpenoids, essential oils, alkaloids, and coumarins. LC-MS investigation reported the presence of Selidin (coumarin) and Tamarixetin (monomethoxyflavone) in the Pigeon Pea Leaves. The present investigations have demonstrated that methanolic extract of Pigeon Pea leaves exhibited impressive antibacterial activity against E. coli and antifungal activity against C. albicans with MIC values 50 µg/ml 250 µg/ml respectively. The extracts studied here have demonstrated to be a new remedial source used against diseases caused by these microorganisms.

Green Extraction of Antioxidant Flavonoids from Pigeon Pea (Cajanus cajan (L.) Millsp.) Seeds and Its Antioxidant Potentials Using Ultrasound-Assisted Methodology.

Pigeon pea is an important pea species in the Fabaceae family that has long been used for food, cosmetic, and other phytopharmaceutical applications. Its seed is reported as a rich source of antioxidants and anti-inflammatory flavonoids, especially isoflavones, i.e., cajanin, cajanol, daidzein, and genistein. In today's era of green chemistry and green cosmetic development, the development and optimization of extraction techniques is increasing employed by the industrial sectors to provide environmentally friendly products for their customers. Surprisingly, there is no research report on improving the extraction of these isoflavonoids from pigeon pea seeds. In this present study, ultrasound-assisted extraction (USAE) methodology, which is a green extraction that provides a shorter extraction time and consumes less solvent, was optimized and compared with the conventional methods. The multivariate strategy, the Behnken-Box design (BBD) combined with response surface methodology, was employed to determine the best extraction conditions for this USAE utilizing ethanol as green solvent. Not only in vitro but also cellular antioxidant activities were evaluated using different assays and approaches. The results indicated that USAE provided a substantial gain of ca 70% in the (iso)flavonoids extracted and the biological antioxidant activities were preserved, compared to the conventional method. The best extraction conditions were 39.19 min with a frequency of 29.96 kHz and 63.81% (v/v) aqueous ethanol. Both the antioxidant and anti-aging potentials of the extract were obtained under optimal USAE at a cellular level using yeast as a model, resulting in lower levels of malondialdehyde. These results demonstrated that the extract can act as an effective activator of the cell longevity protein (SIR2/SIRT1) and cell membrane protector against oxidative stress. This finding supports the potential of pigeon pea seeds and USAE methodology to gain potential antioxidant and anti-aging (iso)flavonoids-rich sources for the cosmetic and phytopharmaceutical sectors.

Synthesis and biological evaluation of cajanonic acid A derivatives as potential PPARγ antagonists.

Four series of cajanonic acid A (CAA) derivatives have been designed and synthesized. The newly prepared compounds have been screened for glucose consumption activity in HepG2 cell lines and PPARγ antagonistic activity in HEK293 cell lines. Compound 26g bearing a tetrahydroisoquinolinone scaffold showed the most potent PPARγ antagonistic and hypoglycemic activities. An oral glucose tolerance test (OGTT) was performed and the results further confirmed that 26g was a potent hypoglycemic agent. In addition, the possible binding modes for compound 26g in the PPARγ protein have been investigated in this study.

Effects and mechanism of Pigeonpea (Cajanus cajan (L.) Millsp.) leaves on proliferation, migration, and tube formation of hypoxic human umbilical vein endothelial cells in vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Pigeonpea (Cajanus cajan (L.) Millsp) leaves (PL) are widely used for treating avascular necrosis of the femoral head. PL has an ideal effect on bone angiogenesis in patients with hormone-induced avascular necrosis of the femoral head and could promote the repair of blood vessels in the necrotic femoral head. Angiogenesis is beneficial to the treatment of myocardial ischemia. PL can be used to treat ischemic heart disease; however, no studies have examined whether it could protect the myocardium against ischemia injury via promoting angiogenesis. AIM: The present study aimed to investigate whether PL could encourage angiogenesis on hypoxic human umbilical vein endothelial cells (HUVECs) and whether estrogen receptor (ER-α), protein kinase B (Akt), and vascular endothelial growth factor (VEGF) (the ischemia injury salvage kinase pathway, phosphoinositide-3 kinase (PI3K)) are involved in this effect. METHODS: A hypoxic HUVEC model was established by culture in the hypoxia incubator. The proliferation ability of HUVECs was determined by the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method, the migration rate of HUVECs was inspected by the Transwell method, the tube formation was evaluated by the Matrigel method, and the expression of PI3K, phosphorylated Akt (p-Akt), and VEGF was detected by Western blotting. RESULTS: The proliferation, migration, and tube formation were promoted by the PL extract on hypoxic HUVECs, and the hypoxia-induced downstream signaling was counteracted, leading to increased expression of PI3K, p-Akt, and VEGF in HUVECs. CONCLUSIONS: The current findings showed that the PL extracts encourage angiogenesis. In addition, the above effects could be mediated via ER-α and PI3K/Akt/VEGF pathways.

Components identification and isomers differentiation in pigeon pea (Cajanus cajan L.) leaves by LC-MS.

A valid and reliable method based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry using electrospray ionization was established to identify chemical constituents in the ethanol extract of pigeon pea leaves. A total of 58 compounds were detected both in positive and negative modes. Among them, 42 compounds, including 16 flavones, 1 flavonol, 5 flavanones, 9 isoflavones, 1 coumarin, 1 lactone, 6 stilbenes, 2 chalcones, and 1 other compound, were unambiguously identified or tentatively assigned in view of the retention time, the molecular formula, as well as the fragmentation patterns. Moreover, eight sets of isomers were differentiated by the ion trap mass spectrometry based on the fragment ion differences or the abundance differences of the same fragment ions. The energy-resolved mass spectrometry in light of the relative abundance of characteristic fragment ions was adopted in the study.

Cajanolactone A, a stilbenoid from cajanus cajan, prevents ovariectomy-induced obesity and liver steatosis in mice fed a regular diet.

BACKGROUND: Visceral obesity and fatty liver are prevalent in postmenopausal women. The stilbene-rich extract of Cajanus cajan (L.) Millsp. has been reported to prevent ovariectomy-induced and diet-induced weight gain in animal models, and stilbenoids from C. cajan are thought to have the potential to prevent postmenopausal obesity and fatty liver. PURPOSE: Cajanolactone A (CLA) is the main stilbenoid from C. cajan with osteoblastogenic promoting activity. This study investigated the potential of CLA to prevent postmenopausal obesity and fatty liver. Underlying mechanisms were also investigated. METHOD: Ovariectomized C57BL/6 mice fed a regular diet were used as mimics of postmenopausal women and given 10, 20, or 40 mg/kg/d of CLA, 0.1 mg/kg/d of estradiol valerate (EV, positive control), or vehicle (OVX) orally for 16 weeks. Mice of the same age subjected to a sham operation were used as control (Sham). Body weights were recorded every 2 weeks for 16 weeks. Body compositions were analyzed via micro-CT. Serum levels of lipids, adipocytokines and aminotransferases were measured using the relevant kits. mRNA levels of genes of interest were detected by RT-qPCR. Proteomic study of perigonadal white adipose tissue (pWAT) was performed using tandem-mass-tags-based proteomic technology combined with Parallel-Reaction-Monitoring (PRM) validation. RESULTS: CLA showed potential equivalent to that of EV to prevent ovariectomy-induced overweight, obesity, dyslipidemia, liver steatosis and liver dysfunction, but did not prevent uterine atrophy. In the liver, CLA significantly inhibited ovariectomy-induced upregulation in expression of lipogenic genes SREBP-1c and ChREBP, and stimulated the mRNA expression of apolipoprotein B gene ApoB. In pWAT, CLA reversed, or partially reversed ovariectomy-induced downregulation in the expression of a number of metabolism- and mitochondrial-function-related proteins, including Ndufa3, Pcx, Pdhb, Acly, Acaca, Aldh2, Aacs and Echs1. In addition, ovariectomy-inhibited mRNA expression of Pdhb, Aacs, Acsm5, Echs1, and Aldh2 genes in pWAT was also reversed. CONCLUSION: CLA was demonstrated to be a potential non-estrogen-like drug candidate for prevention of postmenopausal obesity and fatty liver. The underlying mechanism might involve the inhibition of lipogenesis and promotion of triglycerides output in the liver, and the promotion of metabolism and mitochondrial functions of visceral white adipose tissue.

Effective Production of Phenolic Compounds with Health Benefits in Pigeon Pea [Cajanus cajan (L.) Millsp.] Hairy Root Cultures.

Phenolic compounds in pigeon pea possess various biological properties beneficial to human health. In this study, pigeon pea hairy root cultures (PPHRCs) were developed as an effective in vitro platform for the production of phenolic compounds. A high-productive hairy root line was screened and characterized, and its culture conditions were optimized in terms of biomass productivity and phenolic yield. The comparative profiling of 10 phenolic compounds in PPHRCs and pigeon pea natural resources (seeds, leaves, and roots) was achieved by ultra-high-performance liquid chromatography-tandem mass spectrometry analysis. The total phenolic yield in PPHRCs (3278.44 µg/g) was much higher than those in seeds (68.86 µg/g) and roots (846.03 µg/g), and comparable to leaves (3379.49 µg/g). Notably, PPHRCs exhibited superiority in the yield of the most important health-promoting compound cajaninstilbene acid (2996.23 µg/g) against natural resources (4.42-2293.31 µg/g). Overall, PPHRCs could serve as promising potential alternative sources for the production of phenolic compounds with nutraceutical/medicinal values.

Nutraceutical properties of Leucaena leucocephala, Manihot esculenta, Cajanus cajan and a foliage blend in goat kids infected with Haemonchus contortus.

Protein and condensed tannin-rich foliage (TRF) are potentially useful as nutraceuticals. The main objective of this study was to evaluate the diet and anthelmintic properties of three TRF types both individually and in combination. We hypothesized that synergistic or antagonistic effects on feed and anthelmintic values related to associations between TRF types may occur. Nutritional and anthelmintic characteristics of Leucaena leucocephala, Manihot esculenta, Cajanus cajan and a mixture of the compounds were evaluated using alfalfa pellets as a control. TRF ingredients were combined with Dichantium hay (48 and 52% of dry matter intake respectively) in mixed diets were consumed by Creole goat kids. Measurements were carried out in animals without parasites and in animals artificially infected with Haemonchus contortus. Individual feed intake and the digestibility of each diet was measured along with kid growth. There were no significant differences between the growth rates of pre-infected animals and animals fed mixed diets that included alfalfa. A strong anthelmintic activity is observed with Leucaena leucocephala contrary to other TRFs. This work confirms variable dietary and anthelmintic properties of TRF. The combination of TRF did not have synergistic or antagonistic effects on feed value or the anthelmintic potential of TRF.

Antidepressant-like effects of cajaninstilbene acid and its related mechanisms in mice.

Cajaninstilbene acid (CSA), a bioactive constituent isolated from pigeon pea leaves, exhibited neuroprotective activities in previous studies. The present study aims to evaluate the antidepressant effects of CSA by using behavioral despair models of tail suspension test (TST) and forced swimming test (FST), and a chronic unpredictable mild stress (CUMS) model. CSA (30 or 60 mg/kg), intragastrically administrated for 7 days, could significantly reduce the immobility time of mice in TST and FST. CSA treatment (15 or 30 mg/kg) significantly reversed the depressive-like behavioral changes of mice induced by 3 or 6 weeks CUMS that caused the decrease of sucrose preference, the increase of latency to feed in the novelty-suppressed feeding test, and the increase of immobility time in TST of mice. Furthermore, the related mechanisms of the effect were explored by accessing the metabolite levels of kynurenine pathway of tryptophan metabolism and the expression of some related proteins in cerebral cortex of CUMS mice. Our results showed that the kynurenine pathway was upregulated after CUMS, while the alteration could be significantly reversed by CSA. CSA also reversed the CUMS-induced decrease in the levels of BDNF, PSD-95, p-Akt/Akt and p-mTOR/mTOR. Therefore, the antidepressant-like effects of CSA might be achieved through regulating tryptophan metabolism, promoting BDNF and PSD-95 expression, and activating Akt/mTOR pathway in the cerebral cortex.

Potential for smart food products in rural Myanmar: use of millets and pigeonpea to fill the nutrition gap.

BACKGROUND: The present study examined the potential for 'Smart Food' with respect to contributing to the Sustainable Development Goal 2 of ending malnutrition by 2030, using a small-scale capacity building case study in Oe Be Village, Myingyan district, Mandalay region, Myanmar. Within the study site, refined white rice is the major staple, followed by vegetables and animal source food in inadequate quantities. The protein intake in this particular dry zone community meets only 50% of the daily requirement and even less for those children aged less than 23 months. Therefore, to determine the acceptance and opportunity for legumes and millets which are produced locally, nutritious formulations were introduced for various age groups. In addition, a sensory evaluation of the recipes was conducted to test the acceptance of the nutritious products. RESULTS: Two weeks of the inclusion of millets and pigeonpea in the diets of children aged 6-23 months had a positive impact on wasting, stunting and underweight (P = 0.002, 0.014 and 0.023, respectively). Moreover, the acceptability of these new food products by the children was found to be high. These results indicate an unexplored opportunity for specific millets rich in iron, zinc and calcium, as well as for pigeonpea rich in protein, if prepared in a culturally acceptable way. CONCLUSION: The impact and acceptability of this small scale and short-term intervention indicate the potential for Smart Food products in filling the nutrition gap arising from the traditional food consumption habits in the dry zones of Myanmar. © 2019 Society of Chemical Industry.

Cajanonic acid A regulates the ratio of Th17/Treg via inhibition of expression of IL-6 and TGF-ß in insulin-resistant HepG2 cells.

BACKGROUND: The objectives of the present study are to investigate whether cajanonic acid A (CAA) can reduce insulin resistance (IR) in HepG2 cells and to gain a preliminary understanding of the mechanisms underlying this effect. METHODS: Following induction of IR in HepG2 cells, we tested the regulatory effect of CAA on glucose consumption and evaluated hepatocyte production of IL-6, TGF-ß, and key molecules in the insulin transduction pathway. A transwell co-culturing system was used to assess the effect of CAA on IR in HepG2 cells during the differentiation of CD4+ T cells by calculating the ratio of (Th17)/regulatory T cell (Treg). We evaluated the effect of CAA on the expression of IL-17RC cells and HepG2 cell apoptosis by immunofluorescence and flow cytometry assay. RESULTS: CAA improved dexamethasone-induced reduction in glucose consumption in HepG2 cells, inhibited hepatocyte production of IL-6 and TGF-ß, increased the expression of IL-17RC cell, and increased cellular apoptosis in insulin-resistant HepG2 cells. When co-cultured with CD4+ T cells, insulin-resistant HepG2 cells induced a decrease in the ratio of Th17/Treg, but CAA dampened the effect. Application of IL-6 and TGF-ß, together with CAA, reversed the effect of CAA on insulin-resistant HepG2 cells. Overexpression of IL17R, however, counteracted the effect of IL-6 neutralizing antibody within the culture system. CONCLUSION: CAA can regulate the ratio of Th17/Treg by mediating the expression of IL-6 and TGF-ß in insulin-resistant HepG2 cells.

Prenylated stilbenes and flavonoids from the leaves of Cajanus cajan.

Three new prenylated stilbenes, named as cajanusins A-C (1-3), and one new natural product cajanusin D (4), along with six known derivatives (5-10) were isolated from the leaves of Cajanus cajan. Their structures were fully elucidated by means of extensive spectroscopic methods and comparison with data in the reported literatures. The new compounds of 1 and 2 were evaluated for in vitro cytotoxic activities against a panel of human cancer cell lines.