Background: Hepatocellular carcinoma (HCC) grades second among cancer-related deaths. Rehmanniae Radix (RR) has been exposed to have numerous pharmacological properties. Objectives: To inspect RR leaves extracts pro-apoptotic activities on SMMC-7721 liver cancer cell lines. Materials and Methods: Anti-cancer effect of RR extracts in SMMC-7721 liver cancer cell lines was aged rate of cell apoptosis (AO/EB, 4′,6-diamidino-2-phenylindole [DAPI], and PI staining), ΔΨm (Rh-123 staining), intracellular Reactive oxygen species (ROS) (DCFH-DA staining), quantitative polymerase chain reaction (mRNA expressions of Bax, p53, Bcl-2, caspase-3,-9,-8, IL-6, PI3K/AKT, and mTOR). Results: It has been shown that RR leaf ethanolic extracts suggestively declined cell viability, augmented the rate of cell apoptosis (AO/EB, DAPI, and PI staining), and caused the potential for ΔΨm, and induced over-accumulation of intracellular ROS (DCFH-DA staining) in SMMC-7721 cells after 24 h of exposure. In SMMC-7721 cell lines, we have examined anti-cancer activity to scrutinize the underlying mechanism by assessing the mRNA expressions of Bax, p53, Bcl-2, caspase-3,-9,-8, IL-6, PI3K/AKT, and mTOR. Results displayed the significant inhibition of the apoptosis as stated above related proteins. Conclusion: RR extracts exhibited its potential anti-cancer activity against SMMC-7721 cells by prompting apoptosis-induced cell death and inhibiting PI3K/AKT/mTOR signaling.

Background: Cardiotoxicity is one of the emerging health-care issues worldwide and mortality due to this is increasing exponentially. Oxidative stress, myocardial inflammation, and damage to the cardiac membrane are major causative attributes for this toxicity. Isoproterenol (ISO)-induced cardiotoxicity is a well-established and accepted model to estimate innovative cardioprotective agents, as it exhibits several morphological and biochemical aberrations in the myocardium of rat that is comparable with those detected in clinical practice. Objectives: In the present study, we explored the cardioprotective effect of swerchirin (SW) extracted from Swertia chirayita in the ISO model. Materials and Methods: SW was isolated from S. chirayita, characterized by high-performance thin-layer chromatography-mass spectrometry, ¹H-nuclear magnetic resonance (NMR), ¹³C-NMR, and high-performance liquid chromatography techniques. The in-vitro study was performed for 2,2-Diphenyl-1-picrylhydrazyl and nitric oxide scavenging activity to explore the antioxidant capacity. In silico study was performed to ascertain the binding affinity of SW with antioxidant enzymes. The in-vivo study was performed to explore the cardioprotective activity in the ISO-induced cardiotoxic model. Results: The in vitro studies showed the significant antioxidant potential of SW whereas the in silico study revealed its effective binding into the catalytic pocket domain of superoxide dismutase and catalase. The in vivo study showed a significant improvement in antioxidant enzymes and a reduction in serum glutamic-oxaloacetate transaminase and lipid profile. Further, SW also significantly reversed the histopathological aberrations in a dose-dependent manner. Conclusion: Findings of the study showed a significant cardioprotective effect of SW against ISO-induced cardiac damage.

Background: Green synthesis has attracted the attention of all researchers due to its nontoxic, energy-saving, cost-effective, and eco-sound features. In the last decades, the usage of medicinal plants or herbs in the form of extract has been pursued to synthesize nanosized materials with added potential benefits that are manifested in various sectors. Aim: In the current study, an easy, economical and environmentally friendly one-pot synthesis technique has been proposed to obtain silver nanoparticles (AgNPs) using Acmella oleracea leaf extract. Materials and Methods: Color transition and ultraviolet-visible spectroscopy were availed to assess the formation of bio-mediated AgNPs while Fourier transform infrared (FTIR) was used to detect the functionalities in the leaf extract and the obtained 4-nitrophenol (NPs). Field emission scanning electron microscope (FESEM) analysis was used to analyze the morphological features of the NPs. The AgNPs were analyzed for the imminent antioxidant impact using 2,2-diphenyl-1-picrylhydrazyl test. In addition, the catalytic potential of AgNPs in reducing NP to 4-aminophenol (AP) was explored. Results: The absorption maximum for AgNPs was obtained at 435 nm and the FTIR analysis confirmed the capping of NPs by secondary metabolites of leaf extract with shift in peaks. FESEM analysis revealed the spherical shape of NPs with size ranging from 45 to 60 nm. AgNPs were found to exhibit significant antioxidant potential with IC₅₀ value as 298.69 μg/mL and efficiently reduced NP to AP. Conclusion: The study signified that A. oleracea extract can be employed for the phyto-mediated synthesis of AgNPs with the latent antioxidant and catalytic applications that could be applied in the bio-medical field and environmental remediation in addition to other potential applications.

Background: Brucine is an alkaloid derived from the natural plant seeds of Strychnos nux-vomica, also known as a medicinal herb, and broadly employed in Chinese medicine for liver cancer. Objectives: The main intention of these hypothesis anticancer effects of brucine on 7,12-dimethylbenz(a)anthracene (DMBA)-induced skin cancer in mouse model through phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) regulating signaling pathway via the suppressive effect on cell proliferation and apoptotic pathways in mouse model. Materials and Methods: Brucine action on DMBA-induced mouse skin body weight, tumor volume, histology, biochemical, molecular marker analysis using spectrophotometric, Western blotting, and real-time polymerase chain reaction analysis. Results: Brucine stifled the lipid peroxidation (TBARS), suggestively augmented the levels of antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione), and brought back the status of xenobiotic enzymes (Cyt-p450, Cyt-b5, and glutathione S-transferases). In brucine administered since skin tissues presented the cell proliferative protein marker expression of PI3K, and AKT were downregulated compared to the DMBA-applied skin tumor tissues protein. Further, brucine has downregulated the proliferating cell nuclear antigen, cyclin-D1, and p53 expressions. In the apoptotic expression, markers such as Bcl-2, Bax, caspase-3, and caspase-9 were upregulated compared to the DMBA-induced skin cancer. From these data, we diseased and brucine potential to suppress the proliferative cell markers induces apoptotic expressions. Conclusion: The current search settled that administering brucine chemopreventive and chemotherapeutic effect means for the cancer management in clinical tactic.

Background: The roots of Panax vietnamensis Ha et Grushv. (PV) are used in the preparation of local drugs to treat cardiovascular and cerebrovascular diseases. However, it is still not clear if the saponins extracted from PV show a protective effect against myocardial injury, and if so, what are its primary active ingredients. Materials and Methods: In this study, a rat model of ischemic myocardial injury induced by isoproterenol was established, and the effect of PV saponin extract (PVS) on the heart rate and changes in the S-T segment were studied. The compounds were isolated through chromatographic techniques. H9c2 damaged cells, after induction by H₂O₂, were established and then treated with ocotillol-type ginsenosides at a concentration of 0.5, 1, 3, 10, and 30 μg/mL. Then, the cell viability, rate of cellular apoptosis, and apoptosis-related protein expression levels were detected by MTT assay, flow cytometry, and Western blot analysis. Results: PVS inhibited the elevation in the S-T segment and heart rate in rats with myocardial ischemia induced by isoproterenol. Four ocotillol-type ginsenosides and six dammarane-type ginsenosides were isolated from the PVS. Ocotillol-type ginsenosides compounds 1, 2, and 3 showed the effect of increasing the cell viability of H9c2 cardiomyocytes after induction with H₂O₂, and of them, compound 3 showed the strongest activity. Furthermore, compound 3 significantly inhibited the apoptosis of H9c2 injured cells, decreased the expression level of Bax and caspase 3, and increased the expression level of Bcl-2. Conclusion: PVS shows positive effect against myocardial injury. Compound 3 isolated from PVS protected H9c2 cells from damage caused by H₂O₂ by inhibiting apoptosis. These results will provide an important reference for the treatment of coronary heart disease.

Aim: We aimed to monitor an acid polysaccharide with antioxidant activity. Materials and Methods: Three acidic polysaccharides (DAP-A40, DAP-A60, and DAP-A80) were extracted from D. aurantiacum imbricate by alkaline aqueous solution extraction and ethanol precipitation. The structure characterization and antioxidant activity in vitro and in vivo were examined. Results: The molecular weight (M_W) of three polysaccharides was 1.70 mol⁵ Da, 5.78 mol⁴ Da, and 1.36 mol⁴ Da, respectively, by high-performance gel chromatography. The consequences of infrared spectrum displayed that three polysaccharides enclosed uronic acid and sulfuric acid groups. DAP-A40 and DAP-A60 were collected of α-configuration pyranose. DAP-A80 was composed of β-configuration pyranose. Antioxidant test exhibited that DAP-A80 had outstanding antioxidant activity. The half-maximal inhibitory concentration of DAP-A80 in dipping power and scavenging the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), DPPH, and OH radicals was 163.5 μg/mL, 613.2 μg/mL, 583.2 μg/mL, and 365.1 μg/mL, respectively. The grades of correlation analysis showed that the ability of DAP-A80 to scavenge ABTS, DPPH, and OH radicals was negatively connected with the M_W of polysaccharides and certainly correlated with the content of sulfate group. The results of in vivo experiments exposed that DAP-A80 might knowingly decline the formation of malondialdehyde. High levels of DAP-A80 could evocatively upsurge the activity of superoxide dismutase and GSH-Px in mouse serum. Conclusion: DAP-A80 has an antioxidant effect and can be reconnoitered as a health medicine and food.

Background: Type 2 diabetes mellitus is a progressive polygenic disorder requiring a multi-targeted therapeutic approach. A polyherbal formula (PHF) comprised of four traditional herbs known for their anti-diabetic, anti-oxidant, and hepatoprotective activities were used in this study. Objectives: The purpose of this research was to find out the plausible mechanisms underlying the synergistic effects of PHF in an experimental setting of diabetes mellitus. Materials and Methods: PHF was evaluated for the presence of residual toxins, acute oral toxicity, and its effects on carbohydrate digestive enzymes. PHF (100, 200, and 300 mg/kg/p. o., respectively) was used to treat streptozotocin-induced diabetic rats for 12 weeks followed by glycemic, histopathological, biochemical, and ultrastructural changes measurement. mRNA levels of AMPK, insulin receptor substrate (IRS), phosphoinositide-3-phosphate kinase (PI3K), Akt, and glucose transporter 2 (GLUT2) were measured using real-time polymerase chain reaction. Results: In PHF, the residual toxins were absent. PHF inhibited the α-amylase (IC₅₀ 152.2 ± 9.3 μg/mL), and α-glucosidase (IC₅₀ 103.0 ± 0.81 μg/mL) activities in-vitro. Further, up to a dose of 2000 mg/kg, PHF showed no signs of mortality. PHF treatment significantly maintained the glycemic state, antioxidant status, lipid profile, hepatic-architecture, and ultrastructural alterations in diabetic rats. Similarly, diabetic rats showed detrimental effects on the mRNA level of AMPK and IRS-PI3K-Akt-GLUT2 signaling which were attenuated by PHF treatment. Immunohistochemical analysis also revealed an improvement in p-Akt expression after PHF treatment. Conclusion: In streptozotocin-induced diabetic rats, PHF improves glucose and lipid metabolism by attenuating hyperglycemia, hyperinsulinemia, dyslipidemia, insulin resistance, oxidative stress, inflammation, and deterioration of hepatic architecture possibly through AMPK mediated improvement in hepatic IRS-PI3K-Akt-GLUT2 signaling pathway.

Aim: Cancer is one of the life-threatening diseases which cause severe pathological conditions, leading to mortality. The exhaustive data on the vital role of medicinal plants in combating cancer and related diseases are available since antediluvian times. Materials and Methods: In this present study, cell viability, morphological changes, and IC₅₀ were evaluated by in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltertazoliumbromide) assay. Hydro-alcoholic and ethyl acetate extracts of fruits Annona muricata (AM) and aerial parts Euphorbia tirucalli (ET) against lung (A549, H1975) and oral (SCC9, SCC25) were used to investigate the potential antitumor activity. Results: Ethyl-acetate extract of AM and ET showed the highest IC₅₀ value, 89.48 μg/mL and 119.2 μg/mL against lung cancer cell line A-549. Among four study extracts, the IC₅₀ value of hydroalcoholic extract of AM showed 184.3 μg/mL against H1975 cell line. The hydroalcoholic extract of AM and ethyl acetate extract of EA showed the IC₅₀ value of 149.7 μg/mL and 156.2 μg/mL against SCC9 cell line. Hydroalcoholic and ethylacetate extract of ET showed the highest cytotoxic potency against SCC25 139.2 μg/mL and 205.6 μg/mL compared to AM. Further, all the study extracts exhibited decrease in % cell viability in the dose-dependent manner. Conclusion: This comprehensive data obtained from the in vitro study indicate that the extracts that showed toxicity toward cancer cell lines can be considered potential chemotherapeutic agents. The data suggest to further confirm the anticancer potential by conducting in vitro and in vivo studies, so that the study plants may be adopted in the treatment of lung and oral cancer.

Background: Water dropwort (Oenanthe javanica [Blume] DC.) has been used for the improvement of diverse health disorders in the traditional folk medicine. Objectives: This work aimed to primarily assess the skin anti-aging potential of its aerial parts. Materials and Methods: The dried aerial parts of water dropwort were extracted with water under high pressure and high temperature, which produced the resultant powdered extract, named OJW. The antiradical activity of OJW was quantitated using ABTS^•+ and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) scavenging assays. The in vitro scavenging activities of OJW against superoxide anion radical, hydrogen peroxide and nitrite ions were determined based upon spectrophotometric protocols. The anti-elastase and anti-hyaluronidase activities of OJW were spectrophotometrically determined. Results: The contents of total polyphenols and total flavonoids in OJW were determined to be 13.5 ± 0.3 mg gallic acid equivalent/gram OJW and 16.9 ± 0.1 mg naringin equivalent/gram OJW, respectively. OJW exhibited total antiradical activities in both ABTS^•+ and DPPH scavenging assays. The scavenging activities of OJW on individual Reactive oxygen species, such as hydrogen peroxide and superoxide anion radical, and nitrite ions were convinced. OJW exerted inhibitory activities on elastase and hyaluronidase. Liquid chromatography-tandem mass spectrometry analysis indicated the presence of two flavonoids, quercetin, and isorhamnetin, in OJW. Conclusion: O. javanica aerial parts possess skin anti-aging potential through the antioxidant, anti-inflammatory, and anti-wrinkle activities.

Objectives: In this study, we aimed to study the effect of total flavonoids extracted from Hippophae rhamnoides L. (TFH) on the activity of five CYP450 enzymes in rats by high-performance liquid chromatography (HPLC). We also studied the effect of TFH on the expression of CYP450 enzyme mRNA in rat liver using quantitative real-time PCR (qRT-PCR). Materials and Methods: TFH was orally administered to male rats once daily at doses of 100, 200, and 400 mg/kg/day for 14 days. We established HPLC method to detect the concentration of the analytes in the rat plasma. We used DAS software to calculate the pharmacokinetic parameters. Then, qRT-PCR was used to study the effect of TFH on the expression of CYP450 mRNA. Results: The pharmacokinetic analysis of theophylline in the TFH group revealed a short half-life (t_1/2), a decrease in the area under the curve (AUC), and an increase in the value of plasma clearance (CL) (P < 0.05, P < 0.01). In the case of midazolam, t_1/2 was prolonged, C_max was increased (P < 0.05). Results from the PCR analysis indicate that TFH downregulated the expression of CYP3A4 mRNA and upregulated the expression of CYP1A2 mRNA. Conclusion: In conclusion, TFH might induce the activity of CYP1A2 and inhibit the activity of CYP3A4. Herb–drug interaction should be carefully considered when TFH is being used in combination with drugs metabolized by CYP1A2 and CYP3A4. SUMMARY

• Seabuckthorn is a kind of drug and food homologous substance. Care should be taken when using drugs metabolized by CYP1A2 and CYP3A4 in combination.

[INLINE:1] Abbreviations used: TFH: Total flavonoids of Hippophae rhamnoides L.; t_1/2: Half-life; CYP450: Cytochrome P450; IS: Internal standard; AUC: Area under the curve; qRT-PCR: Quantitative Real-time PCR; CL: Plasma clearance; DDIs: Drug-drug interactions; C_max: Maximum plasma concentration.

Background: Hesperidin and myricetin are anti-inflammatory and anti-oxidant flavonoids that have beneficial effects in fatty liver disease (FLD), but information regarding their effects on cytochrome P450 (CYP450) enzymes in FLD is limited. Objectives: This study determined the impacts of hesperidin and myricetin on CYP450 profiles in FLD mice. Materials and Methods: Adult female mice were fed a high fat diet (HFD, 60 kcal % fat of total food) with daily intragastrically administered ethanol (0.5 g/kg/day) in combination with either fenofibrate (40 mg/kg/day), hesperidin (50 and 200 mg/kg/day), or myricetin (50 and 200 mg/kg/day) for 60 consecutive days. Liver histomorphology was examined by oil red O staining. Hepatic enzyme activity and mRNA expression of CYP1A2, CYP2E1, CYP3A11, CYP3A13, and CYP4A11 were assessed. Results: HFD-induced hepatocellular damage was prevented by low dose hesperidin and myricetin. Expression of Cyp1a2, Cyp2e1, and Cyp4a11 mRNAs as well as CYP2E1 and CYP3A activities was significantly induced by HFD plus ethanol (HE) while Cyp3a13 expression was slightly increased. Fenofibrate and low dose hesperidin prevented HE-induced Cyp1a2 and Cyp2e1 expression while HE-induced Cyp4a11 expression was prevented by all treatments. The expression of Cyp3a13 was extensively suppressed by high-dose hesperidin and myricetin, and CYP2E1 and CYP3A activities were significantly decreased by all treatments. Conclusion: Alteration of CYP450 profiles by high doses of hesperidin and myricetin could lead to drug interactions. Nevertheless, low dose hesperidin prevented dysregulation of CYP450 expression in FLD and is a promising candidate for FLD treatment.

Background: Breast cancer is one of the leading causes of cancer-related death among females in the world. Sesamol, which is an herbal phenolic compound, is investigated for its powerful antioxidant and anticancer motility. Sesamol induces growth arrest and apoptosis in malignant cells. However, its pharmaceutical significance is limited due to poor bioavailability. The self nanoemulsifying drug delivery system (SNEDDS) is a type of lipid nanocarrier system that is suitable for the encapsulation of lipophilic drug molecules. Objectives: In the present study, Sesamol-loaded SNEDDS were developed, identified, and assessed for the enhancement of its in vitro dissolution rate and anticancer efficacy. Materials and Methods: Based on the solubilization potential of sesamol, the oil (Isopropyl myristate, Isopropyl palmitate, Caprylic capric triglycerides, Sesame oil) surfactant (Span 80, and Tween 80), and cosurfactant (Poly Ethylene Glycol 400) were chosen for the formulation of Sesamol-loaded SNEDDS. SNEDDS were prepared by an aqueous titration technique. Developed formulations were characterized and assessed for thermodynamic stability, self nanoemulsification efficiency, droplet size, polydispersity index, zeta potential, surface morphology, refractive index, the percent of transmittance, and drug release profile. Results: In vitro dissolution rate of Sesamol was significantly enhanced from the optimized formulation in comparison with pure drug. The finalized formulation was selected for in vitro anticancer effects in human breast cancer cells (MCF-7) by 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide (MTT) assay. MTT assay suggested remarkable anticancer efficacy of finalized Sesamol-loaded SNEDDS against MCF-7 cells compared with standard (Marketed preparation). Conclusion: The outcome of this study revealed the incredible potential of SNEDDS in the enhancement of in vitro dissolution rate and anticancer efficacy of the poorly soluble drug.

Background: Rheumatoid arthritis is a chronic, common autoimmune disorder identified by progressive dysfunction of joints and cartilage damage. Oxypaeoniflorin (OPA), a Traditional Chinese Medicine monomer, has been reported for potential against inflammation and oxidative stress. Objectives: The objective of the study is to evaluate the potential of OPA against Freund complete adjuvant (FCA)-induced inflammatory pain in experimental arthritic rats. Materials and Methods: FCA was administered in female rats (Wistar strain) to induce polyarthritis, followed by 28 days of oral treatment with either vehicle, leflunomide (10 mg/Kg), or OPA (10, 20, and 40 mg/kg). Various parameters were assessed to determine the effect of OPA on pain and inflammatory pathway. Results: Adjuvant-induced arthritis (AIA)-induced elevated paw withdrawal latency and threshold suggested induction of arthritic pain. However, OPA (20 and 40 mg/kg) treatment diminished arthritic pain reflected by amelioration of hyperalgesia and allodynia. In addition, OPA showed an effective inhibition (P < 0.05) in FCA-induced alterations in alkaline phosphatase, alanine transaminase, aspartate aminotransferase, serum albumin, and C-reactive protein levels. The AIA-induced elevated oxido-nitrosative stress, protein levels of tumor necrosis factor-α, and interleukins in synovial tissue were effectively reduced (P < 0.05) by OPA. Moreover, OPA effectively downregulated (P < 0.05) enhanced nuclear factor-kappa beta (NF-κB), Ikβα, iNOs, and COX-2 mRNA expressions in synovial tissue. OPA also reduced histopathology alteration induced in the tibiotarsal joint by FCA. Conclusion: OPA exerts its antiarthritic property through inhibition of NF-κB/IκBα pathway to downregulate the activation of pro-inflammatory cytokines and inflammatory mediator thus, ameliorated arthritic inflammation and pain.

Background: Polysaccharide biology, whose core is the structure, function, and edible value of polysaccharides, is regarded as the last great scientific frontier outside the field of protein and nucleic acid research. Materials and Methods: In this study, highperformance gelpermeation chromatography, high-performance liquid chromatography, gas chromatography–mass spectrometry, and nuclear magnetic resonance analysis were performed to identify the structure of a new polysaccharide isolated from Lyophyllum decastes (Fr.) Sing (LDS-1). The anticancer and immunomodulatory ability of the polysaccharides (LDS-1) was also investigated. Results: The results showed that the average molecular weight of LDS-1 was 8681 Da, and the ratio between glucose and galactose was 2:1. Structural analysis revealed four (1 →4)-α-D-Glcp moieties with branches at 6-O position, and the branches consisted of two (1 →6)-β-D–Galp moieties. Our results showed that LDS-1 exhibits immunological activity. At a concentration ranging from 2.5 to 25 μg/mL, LDS-1 could distinctly promote the growth of T lymphocyte, B lymphocyte, and RAW264.7 cells; increase the secretion of IgA, IgD, IgE, IgG, IgM, tumor necrosis factor (TNF)-α, TNF-β, and interleukin-2, and enhance the phagocytotic activity of RAW264.7 cells to phagocytize fluorescent microspheres, when compared with the blank control group (P < 0.01). Furthermore, under in vitro conditions, LDS-1 (2.5-20 μg/mL) exhibited significant antineoplastic activity (P < 0.01) against colon cancer cells (CT26.WT) and S180 cells when compared with the blank control group. However, the inhibition effect was different. The research for antineoplastic activity of LDS-1 in vivo indicated that the tumor inhibition rate was 54.32%. Conclusion: In conclusion, the polysaccharides of LDS-1 exhibited good biological activities, which shows that it can be used as an immunomodulator and an antitumor agent.

Background: In Kerala, dry hill agro ecological zone is famous for the commercial cultivation of hill garlic. Vattavada and Kanthalloor panchayaths in Devikulam block of Idukki district, India, are famous for the cultivation of hill garlic. The traditional land races a being cultivated by Muthuva tribes has role in traditional home remedies and fetches better price in market Therefore, we investigated local landraces of garlic (MLPD garlic, MPD garlic, and SGPR garlic) along with two released varieties (Ooty 1 garlic, Yamuna safed 3-garlic) for their chemical composition, bulb morphological traits, and diversity at molecular level. Materials and Methods: Morphological characterization, biochemical parameters analysis, molecular marker analysis using simple sequence repeats, and gas chromatography-tandem mass spectrometer (GC-MS) analysis were performed for five different genotypes of garlic. Results: Significant difference was observed in morphological characterization, biochemical parameters analysis of five different genotypes of garlic. Molecular marker anlalysis results indicated DNA level variation in traditional garlic genotypes and found these garlic having high storability at field level and used in traditional folk medicines preparations. GC-MS analysis results showed MLPD garlic as having 10 total number of active constituents. MPD garlic as having 14 total number of active constituents. SGPR garlic as having six total number of active constituents. Ooty 1 garlic as having 13 total number of active constituents and Yamuna safed 3 garlic having 7 total number of active constituents. Conclusion: This study showed the uniqueness of MLPD garlic and SGPR garlic used in traditional home remedies with high storability at the field level with the presence of high percent of total sulphides and a significant variation at the molecular level.

Background: Crataegus aronia L. Syn: Azarolus (C. aronia) is a hawthorn species and a perennial bush native to Mediterranean regions. It is recognized for its high polyphenol content and potent antioxidant effects. Research was conducted to test the antidepressant activities of an aqueous extract of C. aronia in a chronic, unpredictable, mild stress-induced rat model. Materials and Methods: Thirty-two adult Wistar male rats were divided into four groups: A control group (no stress and no treatment), stress-model group (stress and no treatment), fluoxetine-treated stress group (stress and fluoxetine treatment), and C. aronia-treated stress group (stress and C. aronia treatment). Urine samples were collected at 0, 21, 36, and 51 days. Enzyme-linked immunosorbent assay kits were used to assess serotonin, norepinephrine (NE), and dopamine (DA) levels. Results: There was a decrease in serotonin levels 3 weeks after stress exposure, but urinary NE and DA levels increased. C. aronia significantly (P < 0.001) reversed the depressive-like symptoms in the rats according to the increased urinary levels of serotonin. Moreover, C. aronia also reduced urinary levels of urinary NE and DA. The neuromodulatory effects of C. aronia were comparable to that of fluoxetine. Conclusion: With its active ingredients of anthocyanins and procyanidins, C. aronia exhibits significant antidepressant-like activity in validated stressed rats, which may be related to its neuromodulatory effects on central monoamines.

Background: Prior studies have revealed that crude Vicatia thibertica polysaccharide have the anti-fatigue effect, but the anti-fatigue effect and potential mechanism of purified polysaccharides endure blurred. Objectives: We intended to purify and gauge the anti-fatigue effects of a polysaccharide isolated from Vicatia thibertica polysaccharide 1 (VTP1). Materials and Methods: First, the exercise fatigue model was recognized in Kunming mice. After 14 days of continuous intragastric administration of VTP1 (50, 100, and 200 mg/kg/day), we assessed the anti-fatigue and antioxidant effects of VTP1 on fatigued mice. In addition, the effects of VTP1 on mitochondrial morphology of skeletal muscle of fatigue mice were detected by transmission electron microscopy. Meanwhile, the expression of mitochondrial DNA was noticed. Finally, using Western blot, immunohistochemistry, and real-time quantitative polymerase chain reaction, respectively, to sense the expression of sirttuin1, peroxisome proliferative activated receptor-γ coactivator 1α (PGC-1α), and nuclear respiratory factor 1 (NRF1). Results: VTP1 meaningly extends the time to exhaustion during weight-bearing swimming and improves the endurance and bodyweight of fatigued mice. Furthermore, VTP1 exerts antioxidant effects, reduces creatine kinase, blood urea nitrogen and lactate dehydrogenase in the serum, surges superoxide dismutase and cuts malondialdehyde in the liver. Meanwhile, VTP1 diminishes degeneration of mitochondria in the skeletal muscle of mice with exercise fatigue and improves the biosynthetic efficiency of mitochondria in skeletal muscle. Finally, VTP1 can upregulate the mRNA and protein expression of PGC-1α and NRF1. Conclusion: VTP1 has an anti-fatigue effect, and the effect may be mediated by the PGC-1α/NRF1 signaling pathway.

Background: Trachyspermum ammi is a common spice with vital medicinal properties used in Ayurveda to treat many ailments. Furthermore, natural Honey is said to have high levels of antioxidants and anti-inflammatory properties. While the combination of both T. ammi and Honey is unexplored in anti-atherosclerotic activity. Materials and Methods: Assays guided isolation of carotenoids, phenolics, and tannins were performed by methanol and aqueous extraction from T. ammi seed powder and honey mixture. Phytochemical screening for antioxidant activity (superoxide radical scavenging activity, nitric oxide radical scavenging activity, and 2, 2-diphenyl-1-picrylhydrazyl scavenging activity) and antilipidemic activity by inhibition of low-density lipoprotein (LDL) oxidation were investigated. Sample showing highest activity with lowest IC₅₀ value from antioxidant and antilipidemic activity was further evaluated on RAW 264.7, THP-1 cells for foam cell inhibition activity, anti-proliferation, antiapoptotic activity, and nitric oxide assay. The sample was characterized using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS). Results: Out of the phytochemicals screened, tannin methanol extract (TME) showed the highest antioxidant activity with IC₅₀ value having 7.11 μg/mL in superoxide scavenging assay, the IC₅₀ value of 1.46 μg/mL by nitric oxide scavenging assay, and followed by IC₅₀ value of 20.83 μg/mL in 2, 2-diphenyl-1-picrylhydrazyl activity. The results showed that it also efficiently inhibited LDL oxidation at 240 μg/mL (71.29% at 5 h)., thus inhibiting foam cell development, preventing proliferation, apoptosis, and nitrate production in cultured RAW 264.7 and THP-1 cells. HPLC analysis showed the presence of tannin in the extract. TME was characterized in GC-MS, which showed 13 prominent compounds. Conclusion: The scientific evidence in the present study showed that the TME from T. ammi seed powder and honey act as an antioxidant and antiatherogenic properties in inhibiting foam cell formation. Hence, this phytochemical can be used for the treatment of atherosclerosis.

Background: Lycium barbarum (LB) is a plant species that is well known in Chinese traditional medicine and is also considered a nutrient, belonging to the Solanaceae family, also called goji berry or wolfberry. Objectives: The aim of this study was to investigate the protective efficacy of LB, in kidney damage caused by acute pancreatitis (AP). Materials and Methods: In the study, we used 36 female Wistar albino rats (12 in each group) which were divided into three groups: Control, cerulein (100 μg/kg b. wt. intraperitonally) and Cerulein + LB (6 mg/ml/day gastric gavage) group. Serum lipase, Interleukin (IL)-1, and IL-6 levels were measured. Superoxide dismutase, catalase (CAT), glutathione peroxidase enzyme activity assays and 8-hydroxy deoxyguanosine, malondialdehyde (MDA), and protein levels were measured in kidney tissue samples. In addition, histopathological analysis was performed in kidney tissue samples. Results: According to the findings, in the AP model created with Cerulein, administration of LB plant extract decreased oxidative stress and damage caused by AP in the kidney tissue and partially suppressed the inflammatory reactions in the tissue. Conclusion: According to the findings, in the AP model created with Cerulein, administration of LB extract decreased oxidative stress and in kidney damage caused by AP.

Objectives: Piper nigrum (PN) is well known for its cytotoxic and pharmacological benefits in several cancer cells. However, there is less documented evidence about its cytotoxic efficacy against cholangiocarcinoma (CCA). The roles of PN extract in two CCA cells, KKU-100, and KKU-M452, were evaluated. Materials and Methods: Viability was determined by sulforhodamine B and cell cycle distribution. Apoptotic effects were examined by flow cytometry after staining with Annexin V-FITC and Propidium idodide, JC-1, and Dichlorodihydrofluorescein (DCF-DA) staining. Migration was studied by Wound healing and Matrigel migration assay. Results: The results indicated that PN treatment significantly inhibited cells viability and cell replication by dose-and time-dependent both of two CCA cells. Growth was decreased by detecting the cell cycle arrest at G0/G1 phase in KKU-100 cells and S to G2/M phase in KKU-M452 cells. PN extract markedly induced cancer cells apoptosis after treatment for 24 h by loss of mitochondrial membrane potential and increasing of reactive oxygen species production. Furthermore, a significant reduction of migration was observed in both two cells, KKU-100 cells was suppressed the migratory ability more than KKU-M452 cells. Conclusion: The data demonstrated that PN extract directly suppresses proliferation and inhibits cells migration in two CCA cells. Finally, PN may be useful for CCA treatment.

Background: The cerebral ischemic stroke befalls in response to the abrupt occlusion of blood vessels that leads to deprived oxygen and glucose in brain and causes brain injuries. Stroke is associated with higher morbidity and mortality rate globally. Syringin is a bioactive compound from Eleutherococcus senticosus and possesses plentiful biological actions. Objectives: In this research work, we envisioned to observe the neuroprotective actions of syringin against ischemic-reperfusion (I/R)-provoked ischemic stroke in rats. Materials and Methods: The focal cerebral I/R injuries were roused to the male Wistar rats through the middle coronary artery occlusion (MCAO) technique. The syringin (10, 25, and 50 mg/kg) was administered to the rats through intragastric route for 7 successive days prior to MCAO and another 3 days after MCAO. Sham rats were administered with usual diet. The neurological score and parameters were measured by standard methods. The status of inflammatory cytokines and mediators in both serum and brain tissues was considered by commercial assay kits. The mRNA expression of toll-like receptor (TLR) 4, MyD88, Fas, and FasL was inspected by reverse transcription–polymerase chain reaction technique. Results: The syringin administration to I/R rats established the lessened neurological score and parameters. Syringin supplementation was meritoriously suppressed the levels of the inflammatory cytokine, i.e., interleukin (IL)-1 β, IL-6, and tumor necrosis factor-α and enhanced the IL-10 status in I/R rats. Syringin abridged the inflammatory mediators like cyclooxygenase-2, prostaglandin-2, and nuclear factor kappa B levels in the serum and brain tissues. The mRNA expression of TLR4, MyD88, Fas, and FasL was noticeably downregulated by the syringin. Conclusion: Taken together, our results showed the curative role of syringin against ischemic stroke in rats. Syringin can be an auspicious anti-stroke agent in future to treat ischemic stroke.

Background: Panax ginseng is a perennial medicinal herb also known as Korean ginseng or Insam (인삼), commonly found in Korean Peninsula. These herbs are used to treat different types of diseases. Recent studies have shown that phytochemicals found in P. ginseng harbor anticancer activity against various cancers. However, the biological and molecular mechanisms of these phytochemicals are still unknown in osteosarcoma (OS). Materials and Methods: This study utilized the network pharmacology method comprised target prediction, gene enrichment and ontology, KEGG pathway analysis, and gene expression studies. The obtained results were used to predict the interaction of phytochemicals with the human CDKL3 domain implicated in OS using molecular docking. Toxicity and pharmacokinetic elements of these phytochemicals were also identified. Results: Results showed that Fumarine and Inermin are bioactive phytochemicals that have a multimodal effect on multiple targets and pathways involved in the progression of OS. These compounds were able to regulate the expression of genes and interacted with human CDKL3. These compounds have good pharmacokinetic and toxicological characteristics. However, they exert a high risk of hepatotoxicity. Conclusion: The present study provided a predicted mechanism of action of bioactive phytochemicals of P. ginseng in the inhibition of OS.

Background: Bojanggunbi-tang (BGT) is a well-known combination of ancient Korean herbal medicines and has been widely used for treating gastrointestinal symptoms. Objectives: This study was aimed at investigating whether BGT protects against non-steroidal anti-inflammatory drug (NSAID)-induced small intestinal injury (NSI), by using a murine model of indomethacin-induced NSI. Materials and Methods: NSI was induced in the mice by subcutaneous injections of 15 mg/kg indomethacin. BGT was administered at doses of 50, 150, and 450 mg/kg, while the positive control received sodium alginate. The treatments were orally administered twice, 30 min before and 6 h after the induction of NSI. The body weight, length of small intestine, macroscopic damages, and histological damages were assessed after 24 h of induction. Results: Gross anatomical analysis revealed that BGT inhibited the shortening of the small intestine and reduced the area of ulceration. Histological analysis revealed that BGT lowered the ulceration and inflammation scores. However, there was no difference between the groups with respect to weight loss. Conclusion: BGT ameliorated NSI via its anti-inflammatory and anti-ulcerative properties. The current study suggests that BGT could be a therapeutic option for NSI.

Background and Objectives: Paralemnalia thyrsoides is an octocoral species of the family Nephtheidae. It has established as platform for the production of a varied array of sesquiterpenoids such as africanane, nardosinane, and neolemnane -type compounds. Antiviral and cytotoxic effects of sesquiterpenes from P. thyrsoides were reported. Materials and Methods: The animal sample of P. thyrsoides was repeatedly extracted with organic solvents. Then, the animal extract was fractionated and purified employing different planar chromatographic methods. The chemical structures of all isolated metabolites were identified by employing spectroscopic tools (ultraviolet [UV], IR, and nuclear magnetic resonance) along with MS. The anti-inflammatory activity (membrane stabilization%), and histamine release inhibitory effect, the antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, along with cytotoxic activity against four-cancer cells: hepatocellular carcinoma (Hep G-2), colon (HCT-116), prostate (PC-3), and breast (MCF-7) cancers were evaluated. Results: Three new sesquiterpenoids along with two known ones and a gorgostane steroid. The three new sesquiterpenoids were identified as eudesma-1, 2, 15-trihydroxy-3-en-7-one (1), eudesma-1, 2, 15-trihydroxy-5-ene (2), and nardosinanol J (3). Whereas the known compounds were identified as lemnolin A (4) and gorgostane (5). The in-vitro assays results revealed that the total organic extract showed anti-inflammatory activity (membrane stabilization %) with IC₅₀ of 88.3 ± 1.2 compared to positive control (indomethacin with IC₅₀ of 17.02 ± 1.2 μg/ml) and strong histamine release inhibitory effect with IC₅₀ of 17.94 ± 1.08 compared to a positive control (diclofenac with IC₅₀ of 17.94 ± 1.26 μg/ml). It also showed that the total organic extract has antioxidant activity using DPPH assay with an IC₅₀ of 157.5 ± 4.24μg/ml. Moreover, the total organic extract has strong inhibitory activities against Hep G-2 with an IC₅₀ of 12.1 ± 1.1 μg/ml, HCT-116 with an IC₅₀ of 13.4 ± 1.8 μg/ml, PC-3 with an IC₅₀ of 28.6 ± 2.7 μg/ml, and good inhibitory activity against MCF-7 with an IC₅₀ of 49.0 ± 3.9 μg/ml. Conclusion: The observed bioactivity and the variety of carbon skeletons isolated warrants further work on the constituents of P. thyrsoides.

Background: Lung cancer is the second most predominant reason for cancer deaths globally. It is estimated to be approximately 30% among the cancer deaths. Daidzein (DAZ) is a polyphenolic compound present commonly in soy-based plants and is proven to have various therapeutic properties. Objectives: In this study, we aimed to understand the immunomodulatory activity of DAZ in the mice model with benzo(a)pyrene (B(a)P)-induced lung carcinoma. Materials and Methods: The mice were divided into five groups: Group I served was the control group; Group II animals were challenged with B(a)P; Group III animals were treated with DAZ before challenge with B(a)P; Group IV animals were treated with DAZ after challenging the animals with B(a)P; and Group V animals were treated with DAZ alone till the end of the experimental period. Tumor incidence was calculated, and the following parameters were analyzed: Body weight, lung weight, total number of tumors, percentage of inhibition, immunoglobulin (Ig) levels (immunoglobulin G, immunoglobulin A, and immunoglobulin M), key marker enzymes, and proinflammatory cytokines in both treated and normal mice. The lung tissues were analyzed through the histopathological analysis. Results: According to our results, all the markers that favor the growth of cancer were increased in the lung cancer group. After the administration of DAZ, all the markers returned to their original levels. Conclusion: In conclusion, DAZ protected the cells against the B(a)P-induced inflammatory responses in lung cancer.

Background: Caragana sinica (Buc'hoz) Rehd, which belongs to the legume family, is used to treat a variety of diseases such as gout, high blood pressure, neuralgia, arthritis, and eczema. Morden studies reveal that C. sinica has anti-tumor, anti-viral, anti-hypertensive, immune-stimulatory, immune-suppressive and anti-inflammatory activities. Aims: This study aims to confirm its therapeutic efficacy on contact dermatitis (CD) induced by harmful chemical. Materials and Methods: The dried roots of C. sinica were extracted using 70% ethanol, then the extract was condensed and lyophilized (ethanol extract of C. sinica, [EECS]). We investigated the effects of EECS on skin lesion severities, erythema and melanin indices, skin weights and thicknesses, histopathological changes and cytokine levels in mice with CD induced by 1-fluoro-2,4-dinitrofluorobenzene. In addition, the effects on changes in body weight and spleen body weight ratios were also investigated. Results: EECS relieved skin lesions such as roughness, abrasions, scabs, erythema, and petechia, inhibited thickening of dorsal skin and lowered erythema and melanin indexes in the CD mice. Besides, EECS reduced epidermal hyperplasia and immune cell infiltration into inflamed tissues and reduced levels of Tumor necrosis factor-α, interferon-γ, interleukin-6, and monocyte chemotactic protein-1 (MCP-1) in inflamed tissues. Finally, body weight gains and spleen/weight ratios of CD mice were unaffected by EECS, unlike dexamethasone treatment. Conclusion: These results suggest that C. sinica has potential use as a therapeutic agent for CD and the therapeutic mechanism is different from that of corticosteroids.

Background: Acorus calamus – a critical medicinal plant, is overexploited, leading to population reduction. Establishing an efficient in vitro protocol is essential for the large-scale production of genetically identical plants. Objectives: Development of fast and reliable in vitro regeneration protocol for A. calamus and clonal fidelity assessment of the regenerants using molecular markers. Materials and Methods: Plants were regenerated on Murashige and Skoog medium with different concentrations of growth regulators in two phases – shooting and rooting. Random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) markers were employed to evaluate the genetic stability of in vitro clones. Results: 6 Benzylaminopurine (BAP) at 1.6 and 2.4 mgL⁻¹ was effective for shoot induction, while root induction was superior in indole-3-butyric acid-incorporated medium at 2.5 mgL⁻. Thirteen RAPD and 16 ISSR primers produced 59 and 96 clear, unambiguous, and reproducible bands, respectively. Both the markers revealed a high monomorphism of 96.79% and 95.63% among the regenerants. Nei's genetic distance analysis disclosed a close genetic association (0.000–0.068) among the genotypes. Conclusion: ISSR was better than RAPD markers in clonal fidelity assessment of the regenerants. The in vitro protocol developed is reliable and suitable for the rapid propagation of true-to-type A. calamus plants.

Background: Luteolin (Lut) is a natural flavonoid with low water solubility. Many studies have revealed that its antitumor effect is more understandable. Objectives: Synthesis of glycyrrhizin-coupled bovine serum albumin-loaded Lut nanoparticles (GL-BSA-Lut-Nps) to progress the water solubility, anticancer effect, liver targeting, cycle arrest, induction apoptosis, and regulating the metabolism of Lut. Materials and Methods: The activity screening of GL-BSA-Lut-Nps on Hepatocellular Carcinoma Bel-7402 cells was spotted by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, cell cycle, and apoptosis were measured by flow cytometry. The solubility of GL-BSA-Lut-Nps was evaluated by ultraviolet spectrophotometer. Fluorescein isothiocyanate was employed to label the drug, and the fluorescence intensity of cells after drug uptake was detected under a fluorescence microscope to sense the targeting of GL-BSA-Lut-Nps to tumor cells. The differences of metabolites between Bel-7402 cells treated with GL-BSA-Lut-Nps and the control group were considered by 1 hydrogen-nuclear magnetic resonance metabolomics. Results: The results presented that the GL-BSA-Lut-Nps prepared by solvent removal method had good anti-tumor activity and water solubility in vitro and the No. 4 Lut nanoparticles (GL-BSA-Lut-Nps-4) screened by the MTT method had the best effect. The IC₅₀ of the GL-BSA-Lut-Nps-4 on the Bel-7402 cell inhibition test was 1.999 ± 0.880 mg/mL. The results of cell cycle and apoptosis displayed that the anticancer effect of the prescription is more palpable. The results of the fluorescence original method are proposed to confirm that the experimentally created GL-BSA-Lut-Nps-4 have a liver targeting effect. The study of metabolomics further clarified the metabolic regulation effect of GL-BSA-Lut-Nps-4 on Bel-7402 cells. Conclusion: It delivers a theoretical basis for the development of new high-efficiency and low-toxicity traditional Chinese medicine preparations for liver cancer.

Background: Tick and tick-borne diseases significantly affect the animal husbandry sector worldwide. To overcome this menace, chemically synthesized acaricides are being used. However, these acaricides are toxic to the animals, pose environmental threat and also have led to the development of resistance in ticks. Objectives: Search for safe and efficacious plant-based alternatives to the chemical acaricides and to assess chemical variability among intra-specific germplasms. Materials and Methods: Ageratum conyzoides L. samples were collected from different locations and pharmacognostic analysis was performed. The plant extract was subjected to chromatographic profiling and quantification of three bioactive markers precocene I, precocene II, and caryophyllene oxide followed by in vitro anti-tick activity through the adult immersion test. Results: Precocene I content ranged from 0.001% to 0.019% while precocene II and caryophyllene oxide content varied from 0.003% to 0.11%. In the Indus plain samples, adult tick mortality (%) ranged from 15.0 ± 2.9 to 78.5 ± 4.1, whereas in the Central India, it ranged from 30.0 ± 12.9 to 81.4 ± 7.7 at 8% concentration of plant extract. Precocene II showed weak positive correlation (r = 0.11) with tick mortality. The results indicate that there is considerable variation in the marker compounds content and anti-tick potential of the plant extracts analyzed. There is significant (P < 0.05) variation in marker compound content as well as anti-tick potential of A. conyzoides. Conclusion: The results indicate there apart from the analyzed marker compounds there might be some other phytomolecules playing a role in the tick mortality which needs further investigation.

Background: In the modern era of therapeutics, the proniosomal system has been identified as the most intriguing one among various novel systems, thus considerably enhancing the bioavailability of low-soluble drugs. The current study aimed to study the enhancement of therapeutic efficacy of topotecan (TPT) with curcumin (CUR) coadministration. Materials and Methods: We optimized the preparation of niosomes, concerning concentrations of lecithin, span 60, and cholesterol. Seventeen trials were proposed by the selected design. All these batches were initially evaluated only for entrapment efficacy (EE), vesicle size (VS), and percentage of TPT release by the end of 12 h. Analysis of variance and generated regression equations were assisted to study the significant variables and magnitude of impact. Results: The desirability of 0.893 was achieved with the optimum concentrations of selected independent variables in attaining the highest EE (90.393%), minimum VS (386.264 nm), and percentage of TPT release (98.614% at 12 h). TPT and CUR release from the optimized formulation were found to be anomalous or non-Fickian diffusion, as evident from the n value of Peppas model. The cytotoxic studies demonstrated that TPT and CUR in liposomal and free forms were found to be less cytotoxic on MCF-7 model cells. All these findings indicate that the coadministration of CUR with TPT proniosomes can be a promising strategy to enhance the antitumor treatment.

Background: Thiazide diuretics are one of the most effective, least expensive antihypertensive medicines, however, they are associated with hypokalemia, which can complicate the outcome of care among hypertensive patients. The concurrent administration of a potassium-rich food such as date palm fruits (DPFs) could be an attractive strategy in ameliorating thiazide-induced hypokalemia. The objective of this preliminary study was to investigate the effect of concurrent administration of DPF with hydrochlorothiazide (HCT), a thiazide diuretic on serum potassium level and lipid profile. Materials and Methods: Thirty-six rats were used for this study and were divided into 6 experimental groups comprising control (normal saline), DPF only, HCT, 25 mg/kg plus HCT, 50 mg/kg plus HCT, and 100 mg/kg plus HCT. Animals were dosed daily for 4 weeks and at the end of the experiment, blood samples were collected and allowed to cloth. Subsequently serum were analyzed for potassium levels and lipid profile. Results: Results showed that DPFs produced significant weight loss compared to the control and HCT only groups. Furthermore, serum potassium levels were increased abolishing hypokalemia produced by HCT in all the combination treatments. Total cholesterol, triglyceride, and low-density lipoprotein levels were all attenuated by concurrent treatment with DPFs and HCT. Conclusion: Therefore, the present study demonstrates that co-administration of DPFs with HCT restored serum potassium levels in rats and hence alleviated the attendant HCT-induced hypokalemia.