Protective role of chlorogenic acid in preserving cytochrome-c stability against HFIP-induced molten globule state at physiological pH.

Numerous neurodegenerative disorders are characterized by protein misfolding and aggregation. The mechanism of protein aggregation is intricate, and it is very challenging to study at cellular level. Inhibition of protein aggregation by interfering with its pathway is one of the ways to prevent neurodegenerative diseases. In the present work, we have evaluated the protective effect of a polyphenol compound chlorogenic acid (CGA) on the native and molten globule state of horse heart cytochrome c (cyt c). A molten globule state of this heme protein was achieved in the presence of fluorinated alcohol 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) at physiological pH, as studied by UV-Vis absorption, circular dichroism, intrinsic and ANS fluorescence. We found that at 50 % (v/v) HFIP, the native cyt c transformed into a molten globule state. The same techniques were also used to analyze the protective effect of CGA on the molten globule state of cyt c, and the results show that the CGA prevented the molten globular state and retained the protein close to the native state at 1:1 protein:CGA sub molar ratio. Molecular dynamics study also revealed that CGA retains the stability of cyt c in HFIP medium by preserving it in an intermediate state close to native conformation.

Accumulation of Cadmium in Transplanted Lichen Pyxine cocoes (Sw.) Nyl., with Reference to Physiochemical Variation and Kinetics of Cadmium Biosorption.

The present study aims to signify the role of Pyxine cocoes (Sw.) Nyl. (P. cocoes) as cadmium (Cd) biomonitor in atmosphere. This was achieved by quantifying the amount of Cd accumulated in transplanted P. cocoes, when stimulated with known concentrations of Cd (5µM, 50µM, 100µM, 150µM and 200µM) at increasing intervals of time up-to 40 days. All the five concentrations exhibited increasing trend of accumulation with time. As depicted by Pearson's Correlation (at p < 0.001), anti-oxidative enzymes (superoxide dismutase r= -0.812, ascorbate peroxidase r= -0.802, catalase r= -0.757) and electrical conductivity (r = 0.693) were the most efficient parameters to depict increased Cd presence in atmosphere. In the current study, accumulation of Cd by transplanted lichen has been first time analyzed by biosorption kinetics. The uptake of Cd by P. cocoes followed pseudo-second-order kinetics (range of R22 value was 0.969-0.998). The marker parameters in combination with the ability to accrue Cd fortifies P. cocoes's role as a biomonitor.

Phytochemical Profiling, Anti-Inflammatory, Anti-Oxidant and In-Silico Approach of Cornus macrophylla Bioss (Bark).

The objective of the current study was to evaluate the phytochemical and pharmacological potential of the Cornus macrophylla. C. macrophylla belongs to the family Cornaceae. It is locally known as khadang and is used for the treatment of different diseases such as analgesic, tonic, diuretic, malaria, inflammation, allergy, infections, cancer, diabetes, and lipid peroxidative. The crude extract and different fractions of C. macrophyll were evaluated by gas chromatography and mass spectroscopy (GC-MS), which identified the most potent bioactive phytochemicals. The antioxidant ability of C. macrophylla was studied by 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and 1,1 diphenyl-2-picryl-hydrazyl (DPPH) methods. The crude and subsequent fractions of the C. macrophylla were also tested against anti-inflammatory enzymes using COX-2 (Cyclooxygenase-2) and 5-LOX (5-lipoxygenase) assays. The molecular docking was carried out using molecular operating environment (MOE) software. The GC-MS study of C. macrophylla confirmed forty-eight compounds in ethyl acetate (Et.AC) fraction and revealed that the Et.AC fraction was the most active fraction. The antioxidant ability of the Et.AC fraction showed an IC50 values of 09.54 µg/mL and 7.8 µg/mL against ABTS and DPPH assay respectively. Among all the fractions of C. macrophylla, Et.AC showed excellent activity against COX-2 and 5-LOX enzyme. The observed IC50 values were 93.35 µg/mL against COX-2 and 75.64 µg/mL for 5-LOX respectively. Molecular docking studies supported these in vitro results and confirmed the anti-inflammatory potential of C. macrophylla. C. macrophylla has promising potential as a source for the development of new drugs against inflammation in the future.

Caralluma edulis (Apocynaceae): A Comprehensive Review on its Traditional Uses, Phytochemical Profile and Pharmacological Effects.

Caralluma edulis is a well-known species of the genus Caralluma from Apocynaceae, commonly known as chunga. Caralluma species are mostly succulent perennial herbs, several of which are edible species. The plant has an outstanding therapeutic background in the traditional system of treatment. It has been recommended for the treatment of a number medical disorders such as hypertension, Alzheimer's disease, rheumatism, gastric problems and leprosy. Traditionally the stem was boiled in water and this extract was then used to cure diabetes. The pharmacological effects of C. edulis have also been explored in various in vitro and in vivo experiments. In this regard, the extract of the plant exhibited strong antioxidant, and analgesic activity against inflammation as well as xylene-mediated ear edema as topical effects. The significant anti-hyperlipidemic effect of the plant extract is also reported. However, the extract was found insignificant in the reversal of alloxan-induced diabetes in the rabbit model at test doses. These pharmacological effects are strongly supported by the presence of different bioactive phytochemicals in the plant. These groups of compounds include sterols, terpenoids, flavonoids, and pregnane glycosides. C. edulis is a very potential member of the genus Caralluma with strong traditional history, phytochemistry and phytopharmacology, and needs further exploration for clinically used lead compounds. In this review, we have focused on combining different reported data on the traditional uses of the plant, its phytochemical profile and pharmacological effects in different experimental assay along with subsequent future prospects.

Comparative in-vitro anti-inflammatory, anticholinesterase and antidiabetic evaluation: computational and kinetic assessment of succinimides cyano-acetate derivatives.

This research was planned to synthesize cyano-acetate derivatives of succinimide and evaluate its comparative biological efficacy as anti-inflammatory, anti-cholinesterase and anti-diabetic, which was further validated by molecular docking studies. The three cyano-acetate derivatives of succinimide including compound 23 Methyl 2-cyano-2-(2,5-dioxopyrrolidin-3-yl)acetate, compound 31 Methyl 2-cyano-2-(1-methyl-2,5-dioxopyrrolidin-3-yl)acetate and compound 44 Methyl 2-cyano-2-(1-ethyl-2,5-dioxopyrrolidin-3-yl) acetate were synthesized. The mentioned compounds were checked for in vitro anti-inflammatory, anti-cholinesterase and anti-diabetic (α-amylase inhibition) activity. To validate the in vitro results, computational studies were carried out using molecular operating environment to analyse the BE, i.e. binding energies of all synthesized compounds against the respective enzymes. The Compounds 23, 31, 44 exhibited anti-inflammatory via inhibiting COX-2 (IC50 value of 204.08, 68.60 and 50.93 µM, respectively), COX-1 (IC50 value of 287, 185, and 143 µM, respectively) and 5-LOX (IC50 value of 138, 50.76 and 20, 87 µM respectively). They exhibited choline-mimetic potential, such as compound 23, 31 and 44 inhibited AChE enzyme (IC50 value of 240, 174, and 134 µM, respectively) and BChE enzyme (IC50 value of 203, 134 and 97 µM, respectively). The Compounds 23, 31, 44 exhibited anti-diabetic effect via inhibiting α-amylase enzyme (IC50 values of 250, 106 and 60 µM, respectively). Molecular docking studies revealed that the synthesized compounds have good binding affinity in the binding pockets of AChE, BChE, COX-2, 5-LOX and α-amylase enzyme and showed high binding energies. The synthesized succinimide derivatives, i.e. compound 23, 31, 44 showed marked inhibitory activities against cyclooxygenase, lipoxygenase, α-amylase and cholinesterase enzymes. Among these three, compound 44 and 31 showed strong anti-inflammatory and anti-diabetic activity while they displayed moderate anti-cholinesterase activity supported by molecular docking results.Communicated by Ramaswamy H. Sarma.

Suppression of colorectal carcinogenesis by naringin.

BACKGROUND: Colorectal cancer is the third most malignant cancer worldwide. Despite novel treatment options, the incidence and mortality rates of colon cancer continue to increase in most countries, especially in US, European and Asian countries. Colorectal carcinogenesis is multifactorial, including dietary and genetic factors, as well as lacking physical activity. Vegetables and fruits contain high amounts of secondary metabolites, which might reduce the risk for colorectal carcinogenesis. Flavonoids are important bioactive polyphenolic compounds. There are more than 4,000 different flavonoids, including flavanones, flavonoids, isoflavonoids, flavones, and catechins in a large variety of plant. HYPOTHESIS: Among various other flavonoids, naringin in Citrus fruits has been a subject of intense scrutiny for its activity against many types of cancer, including colorectal cancer. We hypothesize that naringin is capable to inhibit the growth of transformed colonocytes and to induce programmed cell death in colon cancer cells. RESULTS: We comprehensively review the inhibitory effects of naringin on colorectal cancers and address the underlying mechanistic pathways such as NF-κB/IL-6/STAT3, PI3K/AKT/mTOR, apoptosis, NF-κB-COX-2-iNOS, and ß-catenin pathways. CONCLUSION: Naringin suppresses colorectal inflammation and carcinogenesis by various signaling pathways. Randomized clinical trials are needed to determine their effectiveness in combating colorectal cancer.

Anticonvulsant activity of methanolic extract of Withania cogulans in mice.

Mental and neurological diseases including depression, Parkinson's disease, dementia, epilepsy, anxiety disorders and bipolar disorders account for a considerable amount of the world's disease burden. Unfortunately, drugs used in the treatment of neurological diseases are expensive, symptomatic and they produce undesirable side effects. People from different cultures prefer to use medicinal plants for the treatment of various ailments ranging from plain to perplex disorders because they are most affordable, cost effective and easily accessible source of treatment in the primary healthcare system throughout the world. Withania coagulans, an erect grayish under-shrub belongs to family Solanaceae. It is common in Pakistan, East India, Iran and Afghanistan. The objective of this study was to analyze the anti-seizure activity of crude methanolic extract of Withania coagulans fruits (MeWc). For screening of this activity, maximal electroshock seizures model (MES) and chemically-induced seizures models were used. In maximal electroshock seizures test MeWc showed significant dose dependent percent protection against hind-limb tonic extension; significant and dose-dependent increase in latency to myoclonic jerks and tonic clonic convulsions and decrease in seizures duration were observed in PTZ-induced seizures. In strychnine-induced convulsions MeWc significantly increased latency to hind-limb tonic extension and percent protection from death in a dose-dependent manner. Thus, it was inferred from the experiments that extract of Withania coagulans showed anticonvulsant activity.

Lumbar Muscle Activation Pattern During Forward and Backward Walking in Participants With and Without Chronic Low Back Pain: An Electromyographic Study.

OBJECTIVE: The purpose of this study was to investigate the electromyographic activity of lumbar multifidus (MF) and erector spinae (ES) muscle during forward walking (FW) and backward walking (BW) in participants with and without chronic low back pain (CLBP). METHODS: Twenty-one patients with CLBP were recruited from outpatient department of Centre for Physiotherapy and Rehabilitation Sciences, Jamia Millia Islamia. Twenty-one age-matched healthy controls without CLBP were recruited from community. Maximum voluntary isometric contraction (MVIC) was quantified for MF and ES using standard guidelines. Electromyographic activity of MF and ES was recorded using surface electrodes during FW and BW on a motorized treadmill, which was later normalized by respective MVIC's of each muscle. RESULTS: Muscle activity (in percentage MVIC) was determined to be higher for both the muscles during BW. Activity of MF muscle was significantly higher in CLBP patients compared with healthy controls (P < .04). Electromyographic activity of MF and ES was significantly increased during BW (MF: P < .001; ES: P < .001) compared with FW in both healthy and CLBP groups. CONCLUSION: BW leads to greater activation of the paraspinal muscles. Along with global extensor (ES), activity of core extensor (MF) is also higher during BW than FW in both healthy participants and CLBP patients. BW is a more favorable aerobic activity to enhance lumbar paraspinal recruitment. These findings may have important clinical implications in the rehabilitation of CLBP.