[Transdermal patches containing Cassia seed extract applied at the navel for slow transit constipation in rats: therapeutic effect and analysis of the spectrum-effect relationship].

OBJECTIVE: To explore the therapeutic effect of transdermal patches containing Cassia seed extract applied at the navel on slow transit constipation (STC) in rats and explore the spectrum-effect relationship of the patches. METHOD: In a STC rat model established by gavage of compound diphenoxylate suspension for 14 days, the transdermal patches containing low, medium and high doses of Cassia seed extract (41.75, 125.25, and 375.75 mg/kg, respectively) were applied at the Shenque acupoint on the abdomen for 14 days after modeling, with constipation patches (13.33 mg/kg) as the positive control. After the treatment, fecal water content and intestinal propulsion rate of the rats were calculated, the pathological changes in the colon were observed with HE staining. Serum NO and NOS levels and the total protein content and NO, NOS and AChE expressions in the colon tissue were determined. HPLC fingerprints of the transdermal patches were established, and the spectrum-effect relationship between the common peaks of the patches and its therapeutic effect were analyzed. RESULTS: Treatment with the transdermal patches containing Cassia seed extract significantly increased fecal water content and intestinal propulsion rate of the rat models, where no pathological changes in the colon tissue were detected. The treatment also suppressed the elevations of serum and colonic NO and NOS levels and reduction of AChE in STC rats. Twenty-eight common peaks were confirmed in the HPLC fingerprints of 6 batches of Cassia seed extract-containing patches. Analysis of the spectrum-effect relationship showed that autrantio-obtusin had the greatest contribution to the therapeutic effect of the patches in STC rats. CONCLUSION: The Cassia seed extract-containing patches alleviates STC in rats via synergistic actions of multiple active ingredients in the extract, where autrantio-obtusin, rhein, chrysoobtusin, obtusin, obtusifolin, emodin, chrysophanol, and physcion are identified as the main active ingredients.

Application of the galactomannan gel from Cassia grandis seeds for biomedical purposes: Study of the incorporation of collagenases and their release profile.

The galactomannan-based gel from Cassia grandis seeds was used to incorporate Penicillium sp. UCP 1286 and commercial collagenases. Experiments were carried out according to a 23-full factorial design to identify the most significant parameters for the incorporation process. The pH of the incorporation solution (pHi), stirring time (t), and initial protein concentration in the crude extract (PCi) were selected as the three independent variables, and the efficiency of collagenase incorporation (E) and collagenolytic activity (CA) after 360 min as the responses. pHi and PCi showed positive statistically significant effects on E, while CA was positively influenced by pHi and t, but negatively by PCi. The fungi collagenase was released from the gel following a pseudo-Fickian behavior. Additionally, no <76 % of collagenase was efficiently incorporated into the gel retaining a high CA (32.5-69.8 U/mL). The obtained results for the commercial collagenase (E = 93.88 %, CA = 65.8 U/mL, and n = 0.10) demonstrated a pseudo-Fickian behavior similar to the fungi-collagenase. The results confirm the biotechnological potential of the gel as an efficient matrix for the incorporation of catalytic compounds; additionally, the incorporation of collagenases was achieved by retaining the proteases CA and releasing them in a controlled manner.

Anthraquinone Removal from Cassia obtusifolia Seed Water Extract Using Baking, Stir-Frying, and Adsorption Treatments: Effects on the Chemical Composition, Physicochemical Properties of Polysaccharides, and Antioxidant Activities of the Water Extract.

Safety issues of the controversial anthraquinones from Cassia obtusifolia seed water extracts (CWEs) limit its application. This work aimed to remove the anthraquinones of CWEs by baking treatment (BT), stir-frying treatment (ST), and adsorption treatment (AT). Effects of these treatments on the chemical composition, physicochemical properties of polysaccharides, and antioxidant activities of CWEs were analyzed and compared. Results indicated that AT exhibited the best removal effect on the total anthraquinone among the three treatments. After AT, the contents of rhein, emodin, aloe-emodin, and aurantio-obtusin of the CWE were below the limit of detection. In addition, AT increased the contents of neutral sugars in CWEs in comparison to BT and ST. None of the treatments had an obvious influence on the structural characteristics of polysaccharides. However, AT decreased the antioxidant activity of CWEs due to their lower anthraquinone content. In summary, AT was considered as an efficient and simple method to remove anthraquinones, while retaining the features of polysaccharides.

In vitro antimicrobial efficacy of Cassia alata (Linn.) leaves, stem, and root extracts against cellulitis causative agent Staphylococcus aureus.

BACKGROUND: Cellulitis is a common skin disease encountered in medical emergencies in hospitals. It can be treated using a combination of antibiotics therapy; however, the causative agent Staphylococcus aureus has been reported to develop resistance towards the currently used antibiotics. Therefore, the search for more alternative herbal origin antimicrobial agents is critical. AIM: In this study, maceration and Soxhlet extraction of the whole plant of Cassia alata Linn. (leaves, roots, and stem) were performed using four solvents with different polarities, namely n-hexane, ethyl acetate, ethanol and distilled water. The crude extracts were screened using agar well diffusion, colorimetric broth microdilution, grid culture and bacterial growth curve analysis against Staphylococcus aureus. The phytochemicals in the crude extracts were identified using Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: Agar-well diffusion analysis revealed that extraction using ethyl acetate showed the largest inhibition zone with an average diameter of 15.30 mm (root Soxhlet extract) followed by 14.70 mm (leaf Soxhlet extract) and 13.70 mm (root maceration extract). The lowest minimum inhibitory and minimum bactericidal concentration in root Soxhlet extract using ethyl acetate was 0.313 and 0.625 µg µL-1, respectively. Our study proved that crude extract of the plant suppressed the growth of S. aureus as evidenced from a significant regression extension (p < 0.06, p = 0.00003) of lag phase for 6 h after the treatment with increased concentration. Based on the GC-MS analysis, 88 phytochemicals consist of fatty acids, esters, alkanes, phenols, fatty alcohols, sesquiterpenoids and macrocycle that possibly contributed to the antimicrobial properties were identified, 32 of which were previously characterized for their antimicrobial, antioxidant, and anti-inflammatory activities. CONCLUSION: Ethyl acetate crude extract was better than the other investigated solvents. The root and stem of C. alata showed significant antimicrobial efficacy against S. aureus in this study. The remaining 56 out of 88 phytochemicals of the plant should be intensively studied for more medicinal uses.

Standardized Ethanol Extract of Cassia mimosoides var. nomame Makino Ameliorates Obesity via Regulation of Adipogenesis and Lipogenesis in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice.

Obesity is a major cause of conditions such as type 2 diabetes and non-alcoholic fatty liver disease, posing a threat to public health worldwide. Here, we analyzed the anti-obesity effects of a standardized ethanol extract of Cassia mimosoides var. nomame Makino (EECM) in vitro and in vivo. Treatment of 3T3-L1 adipocytes with EECM suppressed adipogenesis and lipogenesis via the AMP-activated protein kinase pathway by downregulating the expression levels of CCAAT/enhancer-binding protein-alpha, peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1, and fatty acid synthase and upregulating the acetyl-CoA carboxylase. EECM inhibited mitotic clonal expansion during early adipocyte differentiation. Oral administration of EECM for 10 weeks significantly alleviated body weight gain and body fat accumulation in high-fat diet (HFD)-fed mice. EECM mitigated adipogenesis and lipid accumulation in white adipose and liver tissues of HFD-induced obese mice. It regulated the levels of adipogenic hormones including insulin, leptin, and adipokine in the blood plasma. In brown adipose tissue, EECM induced the expression of thermogenic factors such as uncoupling protein-1, PPAR-α, PPARγ co-activator-1α, sirtuin 1, and cytochrome c oxidase IV. EECM restored the gut microbiome composition at the phylum level and alleviated dysbiosis. Therefore, EECM may be used as a promising therapeutic agent for the prevention of obesity.

Integrated metabolic and transcriptomic profiles reveal the germination-associated dynamic changes for the seeds of Cassia obtusifolia L.

INTRODUCTION: The seeds of Cassia obtusifolia L. (Cassiae [C.] semen) have been widely used as both food and traditional Chinese medicine in China. OBJECTIVES: We aimed to analyze the metabolic mechanisms underlying C. semen germination. MATERIALS AND METHODS: Different samples of C. semen at various germination stages were collected. These samples were subjected to 1 H-NMR and UHPLC/Q-Orbitrap-MS-based untargeted metabolomics analysis together with transcriptomics analysis. RESULTS: A total of 50 differential metabolites (mainly amino acids and sugars) and 20 key genes involved in multiple pathways were identified in two comparisons of different groups (36 h vs 12 h and 84 h vs 36 h). The metabolite-gene network for seed germination was depicted. In the germination of C. semen, fructose and mannose metabolism was activated in the testa rupture period, indicating more energy was needed (36 h). In the embryonic axis elongation period (84 h), the pentose and glucuronate interconversions pathway and the phenylpropanoid biosynthesis pathway were activated, which suggested some nutrient sources (nitrogen and sugar) were in demand. Furthermore, oxygen, energy, and nutrition should be supplied throughout the whole germination process. These global views open up an integrated perspective for understanding the complex biological regulatory mechanisms during the germination process of C. semen.

Antiproliferative Activity of Green Synthesised Silver Nanoparticles of Cassia Marginata Roxb.

Green synthesised silver nanoparticles (AgNPs) have been identified as a promising new therapy pathway for cancer because of their anti-angiogenic potency. In the present study, CM-AgNPs were biosynthesized using aqueous leaf extract of Cassia marginata Roxb (CM) and were confirmed by spectral studies like UV-Visible and attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic techniques. The structure and shape of the biosynthesized CM-AgNPs were confirmed by scanning electron microscope (SEM), energy-dispersive spectroscopy (EDX), and high-resolution transmission electron microscopy (HR-TEM) with selected area electron diffraction (SAED) studies. The antioxidant activity of the synthesized nanoparticles were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assay methods, and the IC50 values were found to be 19.58 ± 1.62 and 742.33 ± 14.57 µg, respectively. The anticancer activity of CM-AgNPs was evaluated against human breast cancer cell lines MCF-7 and MDA-MB-231 by 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and the IC50 values were found to be 21.02 ± 1.67 and 26.21 ± 0.33 µg/ml, respectively. These results provide promising information about the biosynthesized CM-AgNPs that can be used in the development of novel anticancer drugs.

Green synthesis of silver nanoparticles from Cassia Auriculata: Targeting antibacterial, antioxidant activity, and evaluation of their possible effects on saltwater microcrustacean, Artemia Nauplii (non-target organism).

Due to their huge surface area to volume ratio, metallic nanoparticles are becoming increasingly important in numerous spheres of life. Here, initially, we aimed to evaluate the potential use of Cassia auriculata (CA) extract to synthesize silver nanoparticles (AgNPs). Then, we evaluated its antimicrobial potential and antioxidant capacity, as well as performed in silico analysis, and investigated the possible non-toxic effect of AgNPs on Artemia nauplii. Fourier transform infrared (FTIR) spectroscopy, scanning and transmission electron microscopy (SEM/TEM), energy dispersive spectroscopy (EDX), X-ray diffraction (XRD), and dynamic light scattering (DLS) studies were used to characterize the biosynthesized AgNPs. Our data indicate that Bacillus cereus, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus bacteria were susceptible to the biosynthesized AgNPs, whose effect was concentration-response. With a ZOI of 10 mm, the AgNPs were most efficient against gram-positive B. cereus bacteria at the highest concentration (75 µg/mL). The biosynthesized AgNPs (at 25 to 125 µg/mL) showed good antioxidant activity in the DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) and FRAP (ferric reducing antioxidant power) assays. Oleanolic acid from CA exhibited strong binding affinity and high binding energy to E. coli and B. cereus (-9.66 and - 9.74 kcal/mol) on in silico research. According to the comparative non-toxicity analysis, AgNPs, AgNO3, and CA bark extract had the least toxic effects on A. nauplii, with respective mortality rates of 28.14, 32.26, and 38.42 %, respectively. In conclusion, the current work showed that AgNPs produced from CA bark could be a promising material for diverse applications.

Anti-diabetic and hypolipidemic effects of Cinnamon cassia bark extracts: an in vitro, in vivo, and in silico approach.

The present investigation was aimed to study the anti-diabetic and hypolipidemic potential of Cinnamon cassia (Lauraceae family) bark in streptozotocin (STZ)-induced diabetic rats. The preliminary phytochemical analysis (hexane, petroleum ether, chloroform, ethanol, methanol, and aqueous extracts), GC-MS analysis (ethanol), in vitro (aqueous, ethanol and methanol), in vivo (ethanol) and in silico anti-diabetic activity with hypolipidemic effect of C. cassia bark was analysed. The ethanolic extract of the C. cassia bark has a fine inhibitory activity than the aqueous and methanolic extract. Out of 20 different compounds identified, seven compounds were biologically active, and 9-octadecenoic acid has highly interacted with PPARα/γ in docking studies. The levels of diabetic markers, enzymes, and lipid profiles were altered in STZ-induced rats, but after the treatment of C. cassia, the levels were returned to the normal. The study may prove the ethanolic extract of C. cassia has a powerful anti-diabetic and anti-hyperlipidemic activity.

Simultaneous determination of seven anthraquinones in Cassiae semen by natural deep eutectic solvent extraction.

INTRODUCTION: Anthraquinones are considered to be an important class of bioactive substances in Cassiae semen, and the content of anthraquinones is an essential indicator of the quality of Cassiae semen raw herbal materials. OBJECTIVES: The present study aimed to propose a novel, efficient and effective ultra-high-performance liquid chromatography (UHPLC) method for the simultaneous determination of aurantio-obtusin, aloe-emodin, rhein, obtusin, emodin, chrysophanol and physcion, with the help of natural deep eutectic solvents (NADESs) as extraction solvents. METHODOLOGY: NADESs were introduced to the simultaneous extraction of anthraquinones from Cassiae semen samples. Several NADESs were designed by menthol, choline chloride, d-glucose as hydrogen bond acceptors, with nine different acids and appropriate water as hydrogen bond donors. The parameters affecting the extraction efficiency of seven anthraquinones were demonstrated in detail. RESULTS: Among the obtained NADESs, the highest extraction efficiency was demonstrated by a solution consisting of d-glucose, lactic acid and water with a molar ratio of 1:5:4. The seven anthraquinones were separated on an ACQUITY UPLC® BEH C18 column (2.1 mm × 100 mm, 1.8 µm) and detected within 12 min by a photodiode array (PDA) detector at 254 and 284 nm. The limits of detection and quantitation were from 1.00 to 7.26 µg/l and 3.29 to 24.22 µg/l, respectively. And Cassiae semen sample-based recoveries ranged from 81.13% to 113.78% with the relative standard deviation (RSD) (n = 6) of 1.4% to 10.1%. CONCLUSION: The developed method demonstrated that NADESs were applied successfully to analyse the anthraquinones in Cassiae semen samples collected from different regions in China.

Antibacterial activity of essential oils extracted from the unique Chinese spices cassia bark, bay fruits and cloves.

Spices are widely used in daily life such as diet and have certain activity. Especially in China, spices have been mainly used as condiments for thousands of years in order to improve the sensory quality of food; in addition, they and their derivatives can also be used as preservatives. In this study, three spices with unique Chinese characteristics widely used were selected: cassia bark (bark of Cinnamomum camphora Presl), bay fruits (Laurus nobilis), and cloves (Syzygiumaromaticum). The main components and antibacterial ability of these three spices were analyzed by simulated extraction method. Through headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) analysis, it was determined that the main active compounds in the essential oils of cassia bark, bay fruits and cloves were cinnamaldehyde (78.11%), cinnamaldehyde (61.78%) and eugenol (75.23%), respectively. The agar plate diffusion test and the simulated food culture medium experiment confirmed that the essential oils extracted from the three flavors have antibacterial effects on Listeria monocytogenes, Listeria innocua, Listeria welshimeri, Listeria ivanovii, Listeria grayi and Vibrio parahaemolyticus. The antibacterial activity of different strains has different optimal extraction conditions. Generally speaking, cinnamon essential oil has the strongest antibacterial activity, while laurel fruit has the lowest antibacterial activity. The study proved the antibacterial activity of these three Chinese-specific spices and provided some new ideas and methods for the subsequent research and preparation of natural food additives and food antibacterial agents.

Taguchi design-based synthesis and structural analysis of Cassia galactomannan hydroxypropyl derivative.

Hydroxypropylation is a significant industrial process for diverse applications of polysaccharides. In the present study hydroxypropylation of Cassia gum derived from ruderal Cassia tora species was investigated using Taguchi's L'16 orthogonal array design of experiments. The optimized reaction conditions comprised: reaction temperature 50 °C, time 240 min, sodium hydroxide (0.015 mol), propylene oxide (0.0755 mol) and 60% aq. propane-2-ol. The maximum hydroxypropyl content, 8.43 and 7.71% were achieved using chromic acid titration and 1H NMR spectroscopic analysis respectively in the optimized product. The chemical shift values of substituted hydroxypropyl groups for methyl, methine and methylene protons at 0.98, 3.87 & 3.41 ppm along with respective carbons at δ 18.23, 69.41 & 79.13, and other assignments, 1H and 13C signals, were confirmed by COSY and HSQC correlation spectral analysis. The substituted hydroxypropyl groups, C 6 of the ß-D-1, 4-linked-Manp unit, were established at 66.18 ppm.

Manno-oligosaccharides from cassia seed gum ameliorate inflammation and improve glucose metabolism in diabetic rats.

Functional oligosaccharides show anti-diabetic effects through inflammation regulation with improved glucose metabolism. In this study, novel prebiotics of manno-oligosaccharides from cassia seed gum (CMOS) were incorporated into the diet of streptozotocin (STZ) plus high-fat and high-sugar diet (HFSD)-induced rats. After feeding for 8 weeks, CMOS (300-1200 mg per kg b.w. per d) significantly ameliorated the fasting blood glucose level (7.1-8.2 mmol L-1) as compared with that of the model group (14.2 mmol L-1), where the area under the oral glucose tolerance test curve was decreased by 20.0%-24.5%. Meanwhile, CMOS prevented STZ plus HFSD-induced damage to islet tissue with a clear and integrated morphology and reduced the glucagon/insulin area ratio (by 97.9% for 300 mg per kg b.w. per d CMOS). CMOS also reduced metabolic endotoxemia and maintained intestinal integrity with recovered mRNA expression of Zo-1 and occludin to the normal comparable level. Upon 16S rDNA sequencing, it was found that CMOS regulated the microbiota composition in the cecum with an increased relative abundance of Bifidobacteria, while that of Shigella was decreased. The molecular mechanisms involved in the anti-diabetic effects of CMOS were further studied. CMOS reduced the mRNA expression of Tlr2 and Tlr4 in the intestines of STZ plus HFSD-induced rats. Meanwhile, Nlrp3 associated inflammasome activation in the intestine and liver with glucose metabolism disorder was inhibited by CMOS, resulting in reduced interleukin-1ß secretion (by 38.8-46.4% for CMOS of 300-1200 mg per kg b.w. per d) and inflammation. Furthermore, CMOS regulated the AKT/IRS/AMPK signaling pathway and improved glucose metabolism in the liver. Findings obtained here implicated that CMOS could modulate metabolic-inflammation as a functional dietary supplement.

Indole Alkaloids and Chromones from the Stem Bark of Cassia alata and Their Antiviral Activities.

The Cassia (Leguminosae) genus has attracted a lot of attention as a prolific source of alkaloids and chromones with diverse structures and biological properties. The aim of this study is to screen the antiviral compounds from Cassia alata. The extract of the stem bark of this plant was separated using silica gel, MCI, ODS C18, and Sephadex LH-20 column chromatography, as well as semi-preparative HPLC. As a result, three new indole alkaloids, alataindoleins A-C (1-3); one new chromone, alatachromone A (4); and a new dimeric chromone-indole alkaloid, alataindolein D (5) were isolated. Their structures were determined by means of HRESIMS and extensive 1D and 2D NMR spectroscopic studies. Interestingly, alataindolein D (5) represents a new type of dimeric alkaloid with an unusual N-2-C-16' linkage, which is biogenetically derived from a chromone and an indole alkaloid via an intermolecular nucleophilic substitution reaction. Compounds 1-5 were tested for their anti-tobacco mosaic virus (TMV) and anti-rotavirus activities, and the results showed that compounds 2-4 showed high anti-TMV activities with inhibition rates of 44.4%, 66.5%, and 52.3%, respectively. These rates were higher than those of the positive control (with inhibition rate of 32.8%). Compounds 1 and 5 also showed potential anti-TMV activities with inhibition rates of 26.5% and 31.8%, respectively. In addition, compounds 1-5 exhibited potential anti-rotavirus activities with therapeutic index (TI) values in the range of 9.75~15.3. The successful isolation and structure identification of the above new compounds provided materials for the screening of antivirus drugs, and contributed to the development and utilization of C. alata.

Protective effects of Forsythiae fructus and Cassiae semen water extract against memory deficits through the gut-microbiome-brain axis in an Alzheimer's disease model.

CONTEXT: Fruits of Forsythia suspensa Vahl (Oleaceae) and seeds of Cassia obtusifolia Linne (Caesalpinaceae) have been used to treat inflammation in Asia. OBJECTIVE: We examined the alleviation of memory function in Alzheimer's disease (AD) rats fed Forsythiae Fructus (FF) and Cassiae Semen water extracts (CS) and investigated the mechanisms responsible for the effects. MATERIALS AND METHODS: Thirty Sprague-Dawley male rats had hippocampal infusions of amyloid-ß(25-35) (AD rats; memory deficit), and ten rats were infused with amyloid-ß(35-25) (non-AD rats; no memory deficit). For eight weeks, all rats freely consumed high-fat diets (43% lard) incorporated with 200 mg/kg body weight assigned aqueous herbal extracts: AD-FF, AD-CS, or without extracts AD-CON (control), non-AD (normal-control). RESULTS: Memory impairment was prevented in the AD-FF (0.54 ± 0.06-fold) and the AD-CS rats (0.33 ± 0.04-fold) compared to the AD-CON by inhibiting amyloid-ß deposition to the levels less than one-fourth of the AD-CON group. The hippocampal pAkt→pGSK-3ß→pFOXO1 pathway was attenuated by approximately 3.25-fold in the AD-CON, while AD-FF prevented the attenuation better than AD-CS. The relative intensity of hippocampal tau protein based on ß-actin was suppressed with AD-FF (0.68 ± 0.09) and AD-CS (0.96 ± 0.81), compared to AD-CON (1.19 ± 0.13). AD decreased the abundance of Bacteroidales by 34.2% and Lactobacillales by 23.8% and increased Clostridiales by 181% while the AD-FF, but not the AD-CS, normalised the gut microbiota changes to be similar to the non-AD. DISCUSSION AND CONCLUSIONS: FF improved memory deficits better than CS in an AD-induced rat model. The potential neuroprotective benefits of FF against AD may be applicable to human AD therapy with additional clinical research.

New sesquiterpene dilactone and ß-carboline alkaloid and the α-glucosidase inhibitory activity of selected phytochemicals from Neolitsea cassia (L.) Kosterm.

One new sesquiterpene dilactone, coccinine (1) and one new ß-carboline alkaloid, daibucarboline F (2) together with 10 known compounds; linderane (3), linderalactone (4), pseudoneolinderane (5), linderanlide C (6), linderanine A (7), epicatechin (8), (-)-taxifolin (9), astilbin (10), L-quercitrin (11) and afzelin (12) were isolated from the stems and leaves of Neolitsea cassia (L.) Kosterm (Lauraceae). The structures of (1 and 2) were established by extensive spectroscopic methods and the known compounds were identified by comparisons with data reported in literature. The relative stereochemistry of compound (1) was assigned by X-ray diffraction analysis with Cu-Kα irradiation. Compounds (3-8) and (10) were evaluated for their α-glucosidase enzymatic inhibitory activity. Compounds (4-6), (8) and (10) exhibited inhibition towards α-glucosidase enzymatic activity with IC50 values ranging from 12.10 to 96.77 µM. This is the first report on the isolation of phytochemicals from N. cassia and their bioactivities.

Aurantio-obtusin induces hepatotoxicity through activation of NLRP3 inflammasome signaling.

Aurantio-obtusin (AO) is a major anthraquinone (AQ) compound derived from Cassiae semen (CS). Although pharmacological studies have shown that the CS extracts can serve as effective agents in preclinical and clinical practice, AQ-induced hepatotoxicity in humans has attracted widespread attention. To explore whether AO induces hepatotoxicity and its underlying mechanisms, we exposed larval zebrafish and mice to AO. We found that AO delayed yolk sac absorption, and increased liver area and inflammation in the larval zebrafish. This inflammation was manifested as an increase in liver neutrophils and the up-regulated mRNA expression of interleukin-6 (Il-6) and tumor necrosis factor-α (Tnf-α) in the larval zebrafish. Furthermore, a pharmacokinetics study showed that AO was quickly absorbed into the blood and rapidly metabolized in the mice. Of note, AO induced hepatotoxicity in a gender-dependent manner, characterized by liver dysfunction, increased hepatocyte necrosis with inflammatory infiltration, and up-regulated mRNAs of Il-6, Tnf-α and monocyte chemotactic protein 1(Mcp1) in the female mice after 28-day oral administration. It also highlighted that AO triggered NOD-like receptor protein (NLRP) signaling in the female mice, as evidenced by the increased NLRP3, Caspase-1, pro-IL-1ß, IL-1ß and IL-18. Finally, we found that AO led to a significant increase in potassium calcium-activated channel, subfamily N, member 4 (KCNN4) and reactive oxygen species (ROS) levels, along with decreased nuclear factor kappa B p65 (NF-κB p65), in the female mouse livers. In conclusion, AO induced hepatotoxicity by activating NLRP3 inflammasome signaling, at least in part, through increased KCNN4 and ROS production, and NF-κB inhibition.

Green Synthesis and Characterisation of Silver Nanoparticles Using Cassia tora Seed Extract and Investigation of Antibacterial Potential.

Nanoparticle research is fascinating and getting hold of consequences due to the wide variety of applications in the biomedical field. Green synthesis of nanoparticles is a cost-effective and eco-friendly approach. It can be synthesised using fungi, algae, plant, yeast, bacteria, microbial enzymes etc. Our current research study focuses on the green synthesis of silver nanoparticles using seed extract of Cassia tora. The colour change from yellow to red colour confirms the formation of silver nanoparticles. The synthesised silver nanoparticles were characterised by Ultraviolet-Visible spectroscopy, Fourier-transform infrared (FTIR), X-ray diffraction analysis (XRD), Scanning Electron Microscopy (SEM) and antibacterial efficacy against three different strains were analysed. The surface plasmon resonance of synthesised AgNPs using Cassia tora seed extract shows maximum absorption peak at 423 nm in UV-visible spectroscopy. X-ray diffraction displays the crystalline nature of synthesised AgNPs and they exhibited four distinct peaks at 36.69°, 42.92°, 63.27° and 76.46°. The particle size of synthesised AgNPs observed through SEM was found to be 55.80 nm, 58.97 nm, 61.06 nm, 63.26 nm and 64.80 nm. S.aureus exhibited maximum zone of inhibition of 12 mm and 13 mm when treated with 25 and 50 µl of the synthesised nanoparticles. Thus, the green synthesised silver nanoparticle using Cassia tora seed extract proved to possess strong anti-bacterial activity.

A New Silver Nano-Formulation of Cassia auriculata Flower Extract and its Anti-Diabetic Effects.

BACKGROUND: Treatment of diabetes mellitus (DM) using plant based drugs is advancing and getting much attention in recent years. Cassia auriculata L. is widely used in Indian folk medicine for the treatment of DM. Site-specific targeted plant drug delivery by metallic nanoparticles carriers is a new emerging procedure under research due to its enhanced bioavailability and reduced toxicity. This study was therefore aimed at biosynthesizing a new silver nanoparticle of Cassia auriculata L. flower extract and study its anti-diabetic efficiency in rats. METHODS: The silver nanoparticles were biosynthesized using AgNO3 solution and characterized by spectroscopy, SEM and EDAX analyses. The acute toxicity of this nano-preparation (up to 2000 mg/kg b. wt) was analyzed in rats and the anti-diabetic efficiency (for 50 mg/kg.b.wt and 200 mg/kg.b.wt) was studied in Streptozotocin induced diabetic rats. The diabetic parameters such as; blood glucose, serum protein, liver glycogen, serum lipid profile, serum levels of creatinine, urea, ALT, AST and ALP were analyzed. The histology of the liver, kidney and pancreas was evaluated after staining with Haematoxylin and Eosin. RESULTS: The increased blood glucose in Streptozotocin induced diabetic rats was found to be significantly reduced (p<0.01) in the treated group of rats. The characteristic damage and disorganization in the cells of Streptozotocin induced DM was found to be recovered in the treated group of rats. The alterations in the lipid profile, hyperglycaemia, reduced serum protein and liver glycogen, enhanced liver function and kidney function markers observed in the rats of DM control group were normalized in the treated group of rats. CONCLUSION: The results of this study, proving an efficient anti-diabetic activity of the biosynthesized silver nanoparticles of Cassia auriculata L. flower extract, implies that this nano-preparation may be exploited as an alternative biopharmaceutical agent for treating DM.

Online extraction and enrichment coupling with high-speed counter-current chromatography for effective and target isolation of antitumor anthraquinones from seeds of Cassia obtusifolia.

Traditional bioassay-guided investigation of bioactive compounds from natural products comprises critical steps, such as extraction, repeated column separation, and activity assay. Thus, the development of facile, rapid, and efficient technology is critically important. Here, a HepG2 cell-based extraction method was first developed to rapidly screen potential antitumor compounds from the seeds ofCassia obtusifolia. Then, an online extraction and enrichment-high-speed counter-current chromatography (HSCCC) strategy was fabricated to facilely and efficiently isolate target antitumor compounds, which included direct extraction from solid C. obtusifolia, removal of polar interferences, enrichment of target compounds, and preparative isolation by HSCCC using flow rate stepwise increasing mode. After further purification by Sephadex LH-20 column, five antitumor anthraquinones, aurantio-obtusin, 1-desmethylaurantio-obtusin, chryso-obtusin, obtusin, and questin, were obtained for structural characterization and bioassay verification. The results may not only provide new perspectives for facile and rapid investigation of bioactive compounds from complex natural products, but also offer a scientific basis for the potential applications of C. obtusifolia.