Phytochemical exploration of Neolitsea pallens leaves using UPLC-Q-TOF-MS/MS approach.

Neolitsea pallens (D. Don) Momiyama & H. Hara (Family: Lauraceae), commonly known as Pale Litsea, is an evergreen small tree, distributed in India at altitudes of 1500-3000 m. Traditionally utilized for various purposes, its leaves and bark are used as spices, and the plant is valued in preparing a hair tonic from freshly pressed juice. Secondary metabolites of the leaves have not comprehensively been analysed so far. The objective of the study was to determine the chemical composition of the leaves by analysing their 25% aqueous methanol extract with the aid of ultra-performance liquid chromatography quadrupole time of flight tandem mass spectrometry. Overall, 56 compounds were identified in the study. Phenolics represented by phenolic acids, phenolic glycosides, proanthocyanidins, and flavonoids were the main components of the extract.

In vitro and in vivo anti-inflammatory activity of Cupressus torulosa D.DON needles extract and its chemical characterization.

ETHNOPHARMACOLOGICAL RELEVANCE: Cupressus torulosa (family Cupressaceae), widely distributed in the north western Himalayan region of India, is a coniferous aromatic tree with various traditional uses of its aerial parts. Its needles have been used for anti-inflammatory, anticonvulsant, antimicrobial, and wound-healing properties. AIM OF THE STUDY: The study aimed at investigating the previously unknown anti-inflammatory activity of the hydromethanolic extract of the needles employing in vitro and in vivo assays and scientifically validate traditional claim of their use in treatment of inflammation. Chemical characterization of the extract with the aid of UPLCQTOFMS was also of interest. MATERIALS AND METHODS: C. torulosa needles were first defatted with hexane and sequentially extracted with chloroform and 25% aqueous methanol (AM). Since the presence of phenolics (TPCs, 208.21 ± 0.95 mg GAE/g needles) and flavonoids (TFCs, 84.61 ± 1.21 mg QE/g needles) was observed in the AM extract only, it was chosen for biological and chemical examinations. Acute toxicity of the AM extract on female mice was evaluated following the OECD guideline 423. In vitro anti-inflammatory activity of the AM extract was examined using egg albumin denaturation assay while carrageenan-induced paw edema and formalin-induced paw edema models at doses of 100, 200 and 400 mg/kg po were used to determine the in vivo activity of the AM extract on Wistar rats of either sex. The components of the AM extract were analyzed by UPLC-QTOF-MS method using non-targeted metabolomics approach. RESULTS: AM extract was found to be non-toxic at 2000 mg/kg b.w. with no signs of abnormal locomotion, seizures and writhing. The extract demonstrated promising in vitro anti-inflammatory activity (IC50 160.01 µg/mL) compared to standard diclofenac sodium (IC50 73.94 µg/mL) in egg albumin denaturation assay. In carrageenan-induced paw edema and formalin-induced paw edema tests the extract showed significant anti- inflammatory activity (57.28% and 51.04% inhibition of paw edema, respectively) at the dose of 400 mg/kg p.o. after 4 h in comparison to the standard diclofenac sodium which displayed 61.39% and 52.90% inhibition, respectively, at the dose of 10 mg/kg p.o. after 4 h in these models. A total of 63 chemical constituents, majority of them being phenolics, were found in the AM extract of the needles. Two compounds namely monotropein (iridoid glycoside), (±)12-HETE (eicosanoid) and fraxin (coumarin glycoside) were reported to have anti-inflammatory effect. CONCLUSIONS: For the first time our study demonstrated that hydro-methanolic extract of C. torulosa needles exhibit anti-inflammatory activity thereby supporting their traditional use in the treatment of inflammatory disorders. UPLCQTOFMS assisted chemical profile of the extract was also unveiled.

Bronco T (Shirisadi kasaya), a polyherbal formulation prevents LPS induced septicemia in rats.

OBJECTIVE: Here, Bronco T (BT), a polyherbal formulation developed in 1984 for treating asthma, has been repurposed against septicemia-induced ALI. MATERIALS AND METHODS: Lipopolysaccharides (3 mg/kg BW) were injected intraperitoneally before 24 hours of surgery to assess the cardiorespiratory parameters, blood PaO2/FiO2 and MPO, pulmonary water content and histological changes in the lungs. The pentoxifylline (PTX) (25 mg/kg BW) was used as the positive control and given one hour before LPS. BT was given 3 hours (orally at different doses of 3, 1.5 and 0.75 g/kg BW) before LPS. RESULTS: The LPS treated group showed significant bradypnea, hypotension and bradycardia, through elongated peaks (RR) and (MAP) respectively and finally death after 95 minutes of LPS injection. The PTX and BT (3 g/kg BW) pretreatment significantly prevented these changes (dose-dependent in the BT group). The survival in these groups was maintained up to 190 min after LPS. The Pentoxifylline showed a better response (75%) than Bronco T (72%). In both the treatments, a significant decrease in pulmonary water content and minimal neutrophil infiltration and intact alveoli-capillary membrane was seen in the transverse section (T.S) of the lungs. CONCLUSIONS: Significant improvement was noted in survival time with lesser tissue damage and improved pulmonary function was observed by pre-treating with Bronco T in LPS induced septicemia.

Impact of Nano Preparation of Phytoconstituents in Medulloblastoma.

The conventional cancer treatment strategies from chemotherapy to surgery often lead to inadequate results which in some cases lead to relapsing of the tumor being treated. Medulloblastoma witness 30% relapse rate which is universally fatal among children. Although the treatment of primary medulloblastoma is well established including surgical excision, postsurgical irradiation, and, more recently, chemotherapy, there is no established treatment for its recurrence. Despite efforts to improve its therapy, frequent long-haul survivors have been recorded in the world's medical literature. In this book chapter, we have attempted to focus light on the nano preparation of phytoconstituents as an alternative approach as it has advantage of providing better bioavailability of the compound in terms of crossing the blood-brain barrier and an additional benefit in terms of limited adverse effects of the natural product over the traditional chemotherapeutic approaches. In recent times, biological methods or green approaches in the case of plants have received immense attention due to its safety and lack of contamination in the process. In this chapter, we will explore some plant products that have been incorporated into nanocarriers to improve their bioavailability in this tumor treatment.

Role of Ayurvedic Plants as Anticancer Agents.

The use of natural products has been increasing at a rapid pace, worldwide, with the aim to maintain a healthy lifestyle and to modify one's dietary habits. Ayurveda is a domain that has numerous wealth of information concerning medicinal plants and its part in controlling numerous ailments, such as neoplastic, cardiovascular, neurological plus immunological ailments. The use of such medicinal plants is important for preventing such diseases, especially "cancer" which is the succeeding foremost cause of mortality collectively. Even though abundant developments have been made in the management and control of cancer progression, substantial deficits and scope for advancement still continue to be unchanged. Several lethal adjacent consequences occur throughout the course of chemotherapy. Natural treatments, such as the use of plant-derived products in the treatment of cancer, might reduce the hostile side effects. Presently, a few plant-based products and its phytoconstituents are being utilized for the management of cancer. Here we have focused on numerous plant-derived phytochemicals and promising compounds from these plants to act as anticancer agents, along with their mechanisms of action.

Effect of a dietary supplement on the reduction of lymphedema-progression in mouse tail-cut model.

OBJECTIVE: The aim of our study was to evaluate in vivo, in a mouse tail model of lymphedema, the effects of a dietary supplement, Garlive®, based on hydroxytyrosol from olive leaves, spermidine from rice seeds, hesperidin from citrus fruits and vitamin A. Hydroxytyrosol has anti-inflammatory, antioxidant and antimicrobial activities and inhibits leukotriene B4 generation; spermidine is able to inhibit the production of pro-inflammatory cytokines and mediators; hesperidin inhibits the secretion of pro-inflammatory cytokines: IFN-γ, IL-2, IL-4, IL-10; vitamin A deficiency was shown to induce inflammation and aggravate existing inflammatory states, whereas supplementation with vitamin A could ameliorate inflammation. MATERIALS AND METHODS: The active compounds were included in tablets: 250 mg of olive leaf extract titrated in 10% hydroxytyrosol, 200 mg of citrus fruits extract titrated in 60% hesperidin, 10 mg of rice (Oryza sativa) seeds extract titrated in 1% spermidine and 0.8 mg of vitamin A. Mice of an inbred group were randomly selected and divided in the control group and drug-treated group. The wound necessary for lymphedema generation was made on the tail of each mice 1 cm below the base of the trunk. RESULTS: After surgical intervention, there was a gradual increase in the circumference of both ends of the wound. The control group showed higher increase of tail volume than the drug-treated group. The differences in tail swelling between the control group and the drug-treated group were significantly different. The peak of swelling was anticipated to the 6th day in the drug-treated group, whereas in the control group the peak was reached later on. CONCLUSIONS: The tested drug prevented the induction of swelling from day 5th of wound creation and decreased the duration of swelling, favoring the wound healing.

Scoping review on the role and interactions of hydroxytyrosol and alpha-cyclodextrin in lipid-raft-mediated endocytosis of SARS-CoV-2 and bioinformatic molecular docking studies.

OBJECTIVE: The aim of the study was to show the effect that two naturally occurring compounds, a cyclodextrin and hydroxytyrosol, can have on the entry of SARS-CoV-2 into human cells. MATERIALS AND METHODS: The PubMed database was searched to retrieve studies published from 2000 to 2020, satisfying the inclusion criteria. The search keywords were: SARS-CoV, SARS-CoV-2, coronavirus, lipid raft, endocytosis, hydroxytyrosol, cyclodextrin. Modeling of alpha-cyclodextrin and hydroxytyrosol were done using UCSF Chimera 1.14. RESULTS: The search results indicated that cyclodextrins can reduce the efficiency of viral endocytosis and that hydroxytyrosol has antiviral properties. Bioinformatic docking studies showed that alpha-cyclodextrin and hydroxytyrosol, alone or in combination, interact with the viral spike protein and its host cell receptor ACE2, thereby potentially influencing the endocytosis process. CONCLUSIONS: Hydroxytyrosol and alpha-cyclodextrin can be useful against the spread of SARS-CoV-2.

Do assorted approaches aid in estimation of uronic acids? Case studies on Tinospora sinensis polysaccharides.

Polysaccharides containing uronic acids are of immense biological significance. Colorimetric methods using different chromogens have been explored for uronic acid estimation in polysaccharides but these methods counter numerous difficulties, when neutral sugars are present in substantial amount. The uronic acid content of cold water-soluble polysaccharide (CWSP) and hot water-soluble polysaccharide (HWSP) isolated from Tinospora sinensis, widely known for marked therapeutic significance has been studied. The uronic acid was quantitatively estimated by spectrophotometric methods using carbazole, 3-phenylphenol and 3,5-dimethylphenol (DMP) vis-a-vis gas-liquid chromatography (GLC) analysis. Galacturonic acid in CWSP and HWSP was estimated as 1.41% and 1.20% respectively. The findings bring to light, the efficacy of chromogens and also reveal to what extent, they could be relied upon. The results also indicated higher specificity and selectivity of DMP over carbazole and 3-phenylphenol. However, GLC analysis despite time consuming remains the finest method for precise estimation of uronic acids. Further, GLC analysis of alditol acetates indicated the monosugar composition of L-rhamnose, L-arabinose, D-mannose, D-galactose and D-glucose in molar ratio 0.178, 0.259, 0.140, 1.045 and 98.377 in CWSP and L-rhamnose, L-arabinose, D-xylose, D-mannose, D-galactose and D-glucose in molar ratio 0.608, 0.628, 0.978, 0.227, 0.111 and 97.448 in HWSP respectively.

Effect of vitamin E administration on histopathological changes in rat testes following torsion and detorsion.

INTRODUCTION: Testicular torsion is a medical emergency, especially in male neonates and adolescents. It is a common clinical outcome and a significant urological issue. From the literature, it is evident that the use of antioxidants in the prevention of testicular reperfusion injury following detorsion is conflicting. This study was conducted to investigate the role of vitamin E in testicular reperfusion injury following detorsion. METHODS: Male Wistar albino rats were divided into Groups I, II, III and IV. Only Group IV rats were pre-treated with vitamin E 100 mg/kg body weight for 30 days. Ischaemia was induced manually by rotating the rat testis to 720 degrees clockwise and counter rotating for reperfusion. The testes were fixed in Bouin's fluid and processed for histopathological examination. RESULTS: A significant decrease in the standard tubular diameter and epithelial height was observed in Group III rats compared to those in Groups I and II. However, the seminiferous tubules in Group IV rats showed recovery in the standard tubular diameter and epithelial height when compared with the untreated control groups. CONCLUSION: The results showed that vitamin E, when administered before torsion of the spermatic cord in rats, provided significant protection against acute testicular torsion and detorsion injury.

Evaluation of Chenopodium ambrosioides oil as a potential source of antifungal, antiaflatoxigenic and antioxidant activity.

Essential oil extracted from the leaves of Chenopodium ambrosioides Linn. (Chenopodiaceae) was tested against the aflatoxigenic strain of test fungus Aspergillus flavus Link. The oil completely inhibited the mycelial growth at 100 microg/ml. The oil exhibited broad fungitoxic spectrum against Aspergillus niger, Aspergillus fumigatus, Botryodiplodia theobromae, Fusarium oxysporum, Sclerotium rolfsii, Macrophomina phaseolina, Cladosporium cladosporioides, Helminthosporium oryzae and Pythium debaryanum at 100 microg/ml. The oil showed significant efficacy in inhibiting the aflatoxin B1 production by the aflatoxigenic strain of A. flavus. During in vivo investigation it protected stored wheat from different storage fungi for one year. Chenopodium oil also exhibited potent antioxidant activity when tested by ABTS method. All these observations suggest the possible exploitation of the Chenopodium oil as potential botanical fungitoxicant in ecofriendly control of post harvest biodeterioration of food commodities from storage fungi.

Effect of Asparagus racemosus rhizome (Shatavari) on mammary gland and genital organs of pregnant rat.

Asparagus racemosus (AR) Willd (family Liliaceae) is commonly known as Shatavari. The alcoholic extract of its rhizome was administered orally to adult pregnant female albino rats at a dose of 30 mg/100 g body weight, daily for 15 days (days 1-15 of gestation). The macroscopic findings revealed a prominence of the mammary glands, a dilated vaginal opening and a transversely situated uterine horn in the treated group of animals. The weight of the uterine horns of the treated group was found to be significantly higher (p < 0.001) but the length was shorter (p > 0.01). Microscopic examination of the treated group showed proliferation in the lumen of the duct of mammary gland. It was obliterated due to hypertrophy of ductal and glandular cells. Hyperplasia of the glandular and muscular tissue and hypertrophy of the glandular cells were observed in the genital organs. The parenchyma of the genital organs showed abundant glycogen granules with dilated blood vessels and thickening of the epithelial lining. The oviduct in the treated group showed hypertrophied muscular wall, whereas the ovary revealed no effect of the drug. The results suggest an oestrogenic effect of Shatavari on the female mammary gland and genital organs.

Effect of Momordica charantia on lipid profile and oral glucose tolerance in diabetic rats.

In this study, the methanol extract of Momordica charantia fruit extract was administered to diabetic rats to assess the long term effect of the extract on the lipid profile and the oral glucose tolerance test. Treatment for 30 days showed a significant decrease in triglyceride, low density lipoprotein and a significant increase in high density lipoprotein level. A significant effect on oral glucose tolerance was also noted. Chronic administration showed an improvement in the oral glucose tolerance curve. The effect was more pronounced when the test was done in rats fed the extract on the day of the test compared with tests done in rats which were not fed the extract on the same day.

Semecarpus anacardium L, nuts inhibit lipopolysaccharide induced NO production in rat macrophages along with its hypolipidemic property.

Traditionally S. anacardium is used for rejuvenation, rheumatoid arthritis, fever and neurological disorders. In the present study it was observed that a fraction of S. anacacrdium at dose of 1 mg/100 g body wt, significantly reduced serum cholesterol from 378.87 mg/dl in the rats fed with atherogenic diet (AD) to 197.99 mg/dl (45-52%) in the rats fed with AD diet and increased serum HDL-cholesterol (33-37%). The same fraction also inhibited LPS induced NO production in the culture activated rat peritoneal macrophages in the dose dependent manner with IC50 value at 50 ng/ml of the culture medium. The drug in the above doses was completely safe and non-toxic, (no change in the enzymes), to liver and kidney functions.

Antioxidant property of Smilex china Linn.

Smilex china Linn. (Smilacaceae Syn Liliaceae) has special pharmacognostic feature as its root is multiseriate, with sclerenchymatic pericycle. The alcoholic extract of rhizome of S. china shows significant protection against FeSO4 induced lipid peroxidation in rat liver homogenate, but has no effect on the rate of oxidation of reduced glutathione. This fraction scavenges the superoxide and hydroxyl radicals, but the effect was more towards the removal of superoxide than that of hydroxyl radicals. Thus it could be concluded that rhizome of S. china has strong antioxidant property.

Effect of Semecarpus anacardium nuts on lipid peroxidation.

Alcoholic extract of pericarp showed significant protection against FeSO4 induced lipid peroxidation, as compared with whole native nut and seeds. Mechanism of action may be through metal chelation or activation of endogenous antioxidant enzymes, because the extract did not show hydroxyl and super oxide anion scavenging property. Further in vitro experiments against FeSO4, it did not maintain the level of reduced glutathione.

Effect of N-2-mercaptopropionylglycine in limiting myocardial reperfusion injury following 90 minutes of ischemia in dogs.

Present study was designed to examine the effectiveness of N-2-mercaptopropionyl glycine (MPG) on oxygen free radical (OFR) mediated reperfusion injury. Twenty dogs underwent 90 min of left anterior descending (LAD) coronary artery occlusion followed by 4 h of reperfusion. In control animals (n = 12), 115 ml of saline was infused through left atrium at the onset of reperfusion whereas treated animals (n = 8) received loading dose of MPG (40 mg/kg) infused through left atrium for 1 h followed by maintenance dose (25 mg/kg) for remaining 3 hours. Percentage area of necrosis vis-a-vis area at risk and percentage necrosis in left ventricular mass in MPG treated animals was significantly lower in comparison to control animals. Reperfusion in control group increased the lipid peroxidation and lowered glutathione (GSH) and superoxide dismutase (SOD) activity. MPG treatment significantly lowered the lipid peroxidation whereas GSH and SOD levels in necrotic zone were higher than in control. The above results suggest that MPG can offer a significant cardioprotection against oxidative stress in canine model.

Interaction of Strychnos nux-vomica-products and iron: with reference to lipid peroxidation.

In this paper, it has been investigated that strychnine, the major active principle in the alcoholic extract of the seeds of Strychnos nux-vomica, is responsible for its antilipid peroxidative property. The mechanism of action of this drug is through the chelation of the free iron in the system. It has also been observed that strychnine does not have any pro-oxidant-property, because it does not convert Fe3+ to Fe2+ and vice versa in the reaction system, as has been observed with several other antioxidants.

Molecular approach to ayurveda.

In ayurvedic system of medicine, it is considered that a living system is made of panch-mahabuta, in the form of Vata, pitta and kapha at the physical level and satwa, raja and tama at the mental level. This covers the psychosomatic constitution and commonly known as the Tridosh theory. The imbalance in these body humours is the basic cause of any type of disease manifestation. Till date, several objective parameters have been proposed to monitor the level of these basic humours but none of them is complete. In this exercise, now it is proposed to consider free radical theory of diseases as one of the objective parameters. To be more specific, vata can be monitored in terms of membrane bound signal transduction, pitta as the process of phosphorylation and de-phosphorylation of different proteins (signalling moieties and enzymes) and kapha can be viewed as the degree of gene expression as protein synthesis. This can be correlated with the ojas of the body or total body defence mechanism.

The interaction of Rubia cordifolia with iron redox status: a mechanistic aspect in free radical reactions.

The present publication investigates the antioxidant property and mechanistic aspect of alcoholic extract of R. cordifolia. The extract of R. cordifolia has shown significant inhibitory effect on FeSO4 induced lipid peroxidation. Study with iron redox status showed that R. cordifolia extract reduced or oxidixed; Fe3+ or Fe2+ respectively, in a dose dependent manner. Results with superoxide anion (O2-.) and hydroxyl radical (OH.), showed no radical scavenging activity. The alcoholic extract significantly maintains the reduced glutathione content both in time and dose dependent manner. It also reduced the rate of depletion of reduced glutathione (GSH) level in presence of ferrous sulphate (FeSO4) and cumene hydroperoxide (CHP). On the basis of these observations, it can be concluded that the antioxidant property of R. cordifolia is due to a direct interaction with iron.