Amelioration of Rheumatoid Arthritis by Fragaria nubicola (Wild Strawberry) via Attenuation of Inflammatory Mediators in Sprague Dawley Rats.

Background and Objectives: Fragaria nubicola has never been evaluated scientifically for its anti-arthritic potential despite its use in folkloric systems of medicine. The research was conducted to assess the potential of F. nubicola against rheumatoid arthritis. Materials and Methods: The current study provided scientific evidence by evaluating the effects of plants using an in vivo CFA-induced model of arthritic rats and subsequent microscopic histopathological evaluation of ankle joints along with the determination of paw edema using a digital water displacement plethysmometer. The study also gave insight by determining levels of pro-inflammatory cytokines, matrix metalloproteinase enzymes (MMPs), prostaglandin E2 (PGE2), nuclear factor kappa B (NF-κB), vascular endothelial growth factor (VEGF), and biochemical and hematological parameters. GCMS analysis was also conducted for the identification of possible anti-inflammatory plant constituents. Results: The data showed that F. nubicola-treated groups attenuated the progression of arthritis and paw edema. Microscopic histopathological evaluation validated the anti-arthritic potential by showing amelioration of bone erosion, infiltration of inflammatory cells, and pannus formation. RT-PCR analysis displayed that treatment with F. nubicola down-regulated IL1ß, IL6, TNFα, NF-κB, VEGF, MMP2, MMP3, and MMP9 levels. Moreover, ELISA exhibited a reduction in levels of PGE2 levels in treatment groups. The levels of RBCs, platelets, WBCs, and Hb content were found to be nearly similar to negative control in the treated group. Statistically, a non-significant difference was found when all groups were compared for urea, creatinine, ALT, and AST analysis, indicating the safety of plant extract and fractions at test doses. GCMS analysis of extract and fractions showed the existence of many anti-inflammatory and antioxidant phytochemicals. Conclusion: In conclusion, F. nubicola possessed anti-arthritic properties that might be attributed to the amelioration of MMPs and pro-inflammatory cytokines.

Bioactivity-Guided Isolation and Antihypertensive Activity of Citrullus colocynthis Polyphenols in Rats with Genetic Model of Hypertension.

Background and Objectives: Citrullus colocynthis belongs to the Cucurbitaceae family and is a wild medicinal plant used in folk literature to treat various diseases. The purpose of the current study was to explore the antihypertensive and antioxidant potentials of Citrullus colocynthis (CC) polyphenol-rich fractions using a spontaneous hypertensive rat (SHR) model. Materials and Methods: The concentrated aqueous ethanol extract of CC fruit was successively fractioned using solvents of increasing polarity, i.e., hexane, chloroform, ethyl acetate and n-butanol. The obtained extracts were analyzed for total phenolic content (TPC), total flavonoid content (TFC) and total flavonol content (TOF). Moreover, the CC extracts were further evaluated for radical scavenging capacity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) assays and antioxidant activity using inhibition of linoleic acid peroxidation and determination of reducing potential protocols. The phytochemical components were characterized by HPLC-MWD-ESI-MS in positive ionization mode. Results: The results showed that ethyl acetate fraction (EAF) exhibited a higher content of phenolic compounds in term of TPC (289 mg/g), TFC (7.6 mg/g) and TOF (35.7 mg/g). EAF showed higher antioxidant and DPPH and ABTS scavenging activities with SC50 values of 6.2 and 79.5 µg/mL, respectively. LCMS analysis revealed that twenty polyphenol compounds were identified in the EAF, including phenolic acids and flavonoids, mainly myricetin and quercetin derivatives. The in vivo antihypertensive activity of EAF of CC on SHR revealed that it significantly decreased the mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressures (DBP) and pulse pressure (PP) as compared to normal and hypertensive control groups. Moreover, EAF of CC significantly reduced the oxidative stress in the animals in a dose-dependent manner by normalizing the levels of superoxide dismutase (SOD), malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide (NOx) and total antioxidant capacity (TAC). Furthermore, the treatment groups, especially the 500 mg of EAF per kg body weight (EA-500) group, significantly (p ≤ 0.05) improved the electrocardiogram (ECG) pattern and pulse wave velocity (PWV). Conclusion: It was concluded that the EAF of CC is a rich source of polyphenols and showed the best antioxidant activity and antihypertensive potential in SHR.

Antioxidant, Anti-Obesity, and Hypolipidemic Effects of Polyphenol Rich Star Anise (Illicium verum) Tea in High-Fat-Sugar Diet-Induced Obesity Rat Model.

Star anise (Illicium verum Hook. fil.) is commonly utilized as a culinary and medicinal fruit and is most famous in indigenous systems of medicine. The present research work aims to appraise and validate the potential of polyphenol-rich star anise tea (SAT) on oxidative stress, obesity and related biochemical parameters in high-fat-sugar-diet (HFSD)-induced obesity model in rats. SAT was prepared using the traditional method in warm water. The Reverse Phase High Pressure Liquid Chromatography (RP-HPLC) analysis was performed for the simultaneous determination of phenolic acids and flavonoids in SAT. Two doses (250 and 500 mg/kg body weight) were selected to investigate the anti-obesity potential of SAT using HFSD-induced obese rat model. Major (>5 mg/100 mL) phenolic acids in SAT were p-coumeric acid, gallic aid, cinamic acid, chlorogenic acid and ferulic acid while catechin and rutin were the major flavonoids detected in the SAT. SAT exhibited 51.3% DPPH radical scavenging activity. In vivo study showed that higher doses of SAT (500 mg/kg body weight) significantly reduced the body weight increase (74.82%) and BMI (0.64 g/cm2). Moreover, significant reductions in the levels of serum total cholesterol, triglyceride, LDL and VLDL were recorded in all the treatment groups in comparison to the HFSDC group. Furthermore, SAT reduced the alterations in MDA, SOD and GSH levels of experimental groups thus showing the potential against oxidative stress. The SAT-500 group showed a significant decrease in the elevated kidney and liver weights and atherogenic index in comparison to the HFSDC group. The present study proved that SAT exhibited strong protective effects against obesity and oxidative stress, especially at higher doses.

Variation in Phenolic Profile, Antioxidant, and Anti-Inflammatory Activities of Salvadora oleoides Decene. and Salvadora persica L. Fruits and Aerial Part Extracts.

(1) Background: The objective of this study was to investigate the potential of Salvadora oleoides (S. oleoides) and Salvadora persica (S. persica) polyphenols as antioxidant and anti-inflammatory agents. (2) Methods: Aerial parts and fruits of S. oleoides and S. persica were collected from the periphery of District Bhakkar, Punjab, Pakistan. Methanol extracts were prepared using the Soxhlet extraction technique. Extract yield varied from 8.15 to 19.6 g/100 g dry plant material. RP-HPLC revealed the detection of thirteen phenolic aids and five flavonoids. Gallic acid, hydroxy benzoic acid, chlorogenic acid, and cinamic acid were the major phenolic acids, whereas catechin, rutin, and myricetin were the flavonoids detected. (3) Results: Maximum total phenolic contents (TPCs) (22.2 mg/g of dry plant material) and total flavonoid contents (TFCs) (6.17 mg/g of dry plant material) were found in the fruit extract of S. persica, and the minimum TPC (11.9 mg/g) and TFC (1.72 mg/g) were found in the aerial part of S. oleoides. The fruit extract of S. persica showed the highest DPPH radical scavenging activity. In vivo anti-inflammatory activity of all the extracts was performed on albumin-induced rat paw edema that was comparable with the standard indomethacin; S. persica fruit extract showed remarkable anti-inflammatory activity. Analgesic activity of aerial part and fruit extracts of S. oleoides and S. persica was investigated using a mouse model, and the results showed that maximum possible analgesia of fruit extracts of S. persica was 53.44%, which is better than the PC group (52.98%). (4) Conclusions: The variations in the antioxidant, anti-inflammatory, and analgesic activities of methanolic extracts of S. oleoides and S. persica were found to be significant, and they have therapeutic potential as antioxidant, analgesic, and anti-inflammatory agents.

A Narrative Review on the Phytochemistry, Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine.

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant's extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.

ANTIOXIDANT ACTIVITY AND FREE RADICAL SCAVENGING CAPACITY OF L-ARGININE AND NAHS: A COMPARATIVE IN VITRO STUDY.

In the family of gaseous transmitters, hydrogen sulfide (H2S) is considered as third member beside nitric oxide (NO) and carbon monoxide (CO), which can play physiological role in different organs. The present study was designed to elucidate the antioxidant and free radical scavenging potentials of L-arginnine (a source for endogenous production of NO in vivo) and NaHS (a source H2S) individually and in combination. Different assays like 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, percent inhibition of linoleic acid peroxidation and reducing power assays were used to evaluate the free radical scavenging capacity and antioxidant activity of L-arginine and NaHS. Furthermore, study was aimed to know the antioxidant potential of both compounds at their effective doses in human body, which is 56 µM for H2S and 1.2 g/mL for L-arginine. The study also aimed to clear whether either NaHS, L-arginine or the mixture of NaHS and L-arginine in vitio (in the form of new compounds) is responsible for their therapeutic action. Results showed that NaHS, L-arginine and combination of NaHS + L-arginine showed good radical scavenging activity i.e., 55.60%, 52.10% and 52.32%, respectively. Moreover, NaHS was found to have ability to inhibit linoleic acid peroxidation by 53.98% at effective dose while L-arginine did not show inhibition of linoleic acid peroxidation. Combination of NaHS + L-arginine showed 54.15% inhibition of linoleic acid peroxidation, which is similar to that of H2S. Reducing power of NaHS was 0.073 and L-arginine showed 0.037, combination of NaHS + L-arginine showed 0.063. It can be concluded that NaHS showed better antioxidant potential in vitio as compared to L-arginine and the antioxidant activity of the mixture of NaHS + L-arginine is closed to the antioxidant activity of NaHS, which reflects that NaHS is a dominant factor in combination mixture that is responsible for antioxidant activity.

Potential of silver against human colon cancer: (synthesis, characterization and crystal structures of xylyl (Ortho, meta, &Para) linked bis-benzimidazolium salts and Ag(I)-NHC complexes: In vitro anticancer studies).

BACKGROUND: Since the first successful synthesis of Ag(I)-N-heterocyclic carbene complex in 1993, this class of compounds has been extensively used for transmetallation reactions where the direct synthesis using other metal ions was either difficult or impossible. Initially, silver(I)-NHC complexes were tested for their catalytic potential but could not get fame because of lower potential compare to other competent compounds in this field; however, these compounds proved to have vital antimicrobial activities. These encouraging biomedical applications further convinced researchers to test these compounds against cancer. The current work has been carried out with this aim. RESULTS: N-ipropylbenzimidazole was synthesized by reaction of benzimidazole with ipropyl bromide. The subsequent treatment of the resulting N-alkylbenzimidazole with ortho/meta/para-(bromomethylene) benzene afforded corresponding bis-benzimidazolium bromides (5-7). The counter anion (Br-) of each salt was replaced by hexaflourophosphate (PF6-) for the ease of handling and further purification (8-10). Each salt (Ligand), in halide form, was further allowed to react with Ag2O with stirring at room temperature for a period of two days to synthesize dinuclear Ag(I)-NHC complexes (11-13). All synthesized compounds were characterized by spectroscopic techniques and microanalysis. Molecular structures of compounds 5, 9 &10 were established through single crystal x-ray diffraction technique. All the compounds were assessed for their anti-proliferation test on human colorectal cancer cell line (HCT 116). Results showed that the ligands (5-10) showed mild to negligible cytotoxicity on HCT 116 cells whereas respective silver complexes (11-13) exhibited dose dependent cytotoxicity towards the colon cancer cells with IC50 ranges between 9.7 to 44.5 µM. Interestingly, the complex 13 having para-xylyl spacer was found the most active (IC50 9.7 µM) that verifies our previously reported results. CONCLUSIONS: All the bis-benzimidazolium salts (8-10) were found inactive whereas after bonding with silver cations, the Ag(I)-NHC complexes (11-13) showed a dose dependent cytotoxic activity. This proved that silver practice an important role in death of cancer cells. Also, the N-alkyl/aryl substitutions and ortho/metal/para xylyl units regulate the cytotoxicity.

Synthesis, characterization, biological evaluation and QSAR of some Schiff base esters: promising new antitumor, antioxidant and anti-inflammatory agents.

We report the synthesis, characterization, biological evaluation and quantitative structure-activity relationship of some Schiff base esters as promising new antitumor, antioxidant and anti-inflammatory agents. The Schiff base esters were synthesized by two synthetic routes using variably substituted hydroxy benzaldehydes with para amino phenol in appreciable yields. All the newly synthesized esters have been characterized by (1)H-NMR,(.13)C-NMR, FT-IR techniques and elemental analysis. The synthesized esters were examined for antioxidant, antitumor and anti-inflammatory potentials through different bioassays and quantitative structure-activity relationship was studied. Bioassays showed encouraging results and indicated that some of these title compounds may have potential for further pharmacological investigations.