Assessment of antiarthritic potential of Asparagus dumosus using formaldehyde and CFA-induced arthritic models in rats via modulation of oxidative stress biomarkers and mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2.

Medicinal plants play a pivotal role in the prevention of chronic non-communicable diseases including arthritis. Despite the traditional use of Asparagus dumosus in arthritis, it has not been studied yet for its effectiveness in arthritis. This study was aimed to explore the antiarthritic potential of A. dumosus in formaldehyde and complete Freund's adjuvant (CFA)-induced arthritic rats. Body weight, arthritic index, hepatic oxidative stress, hematological, biochemical and inflammatory markers were assessed using ELISA, whilst qRT-PCR studies were carried out for the mRNA expression of IL-1b, IL-6, RANKL, OPG, TNF-α and COX-2 genes. GCMS and HPLC analysis were performed to identify the secondary metabolites of A. dumosus. From day 8 to 28 post-administration of formaldehyde and CFA, oral administration of A. dumosus (600, 300 and 150 mg/kg) showed a noteworthy improvement (p < 0.001) in the body weights, immune organ weights, serum levels of rheumatoid (RA) factor, C-reactive protein, TNF-α and IL-6 levels in arthritic rats similar to the effect of piroxicam and methotrexate. Subsequently, the administration of A. dumosus to formaldehyde and CFA-challenged rats, caused a marked decrease (p < 0.001) in the mRNA expression of IL-1b, IL-6, OPG, RANKL, TNF-α and COX-2 genes in treated rats. Likewise, when assessed for antioxidant potential, A. dumosus produced a pronounced (p < 0.001) reduction in malondialdehyde (MDA) levels and hydrogen peroxide (H2O2) production, whilst a dose-dependent (p < 0.001) increase in catalase (CAT) and superoxide dismutase (SOD) activities was recorded. GCMS profiling of A. dumosus presented benzaldehyde, 3-hydroxy-4-methoxy-, 1-decanol and undecane as plant compositions, whereas HPLC fingerprinting displayed quercetin, benzaldehyde, 3-hydroxy-4-methoxy-, gallic acid and cinnamic acid as plants constituents. These results depict that A. dumosus possesses anti-arthritic effect mediated possibly through attenuation of arthritic indices, chronic inflammatory and oxidative stress biomarkers along with down-regulation in the mRNA expression of arthritic candid genes.

Novel antiarthritic mechanisms of Azelaic acid against CFA-induced arthritis in rats by modulating pro- and anti-inflammatory cytokines network.

An immunologic system attacking the body's own tissues is a hallmark of autoimmune disorders, which encompass a wide range of unique conditions. Numerous essential biologic functions, including the regulation of the immune system, inflammation, cell division, and tissue repair, are carried out by cytokines. Natural compounds are an effective treatment for autoimmune illnesses by modulation of inflammatory cytokines and infiltration of leukocytes into the inflamed tissue. Here, anti-arthritic study was carried out using oral administration of Azelaic acid (AzA) for 28 days with doses (20, 40, and 80 mg/kg) in Complete Freund's Adjuvant (CFA) induced arthritis model. AzA ameliorated the adjuvant-induced arthritis by decreasing arthritic score, paw volume, improved body-weight alterations and serum levels of PGE2, 5-LOX and anti-ccp. AzA showed significant down regulation of NF-κB, COX-II, TNF-α, IL-17, IL-1ß, IL-6, and up regulation of IL4 and IL10. Hemoglobin and RBCs count remarkably increased and ESR, CRP, platelets, WBCs levels markedly reduced in post treatment. In addition, the weakened SOD (superoxide dismutase), Catalase (CAT), Glutathione (GSH) activity and the increased levels of malondialdehyde (MDA) were all reversed by AzA treatment. And showed improved radiographical and histologic alterations in the structure of the joints. Molecular docking studies targeting COX-II, iNOS, TNF-α, 5-LOX, IL4, IL10, IL-6, and IL-17 establish a correlation between theoretical and experimental results. Results showed that AzA inhibit pro-inflammatory cytokines (COX-II, TNF-α, 5-LOX, IL-17, NF-κB, IL-1ß, and IL-6) and increase anti-inflammatory cytokines, which supported the anti-arthritic and immunomodulatory potential of AzA.

Molecular insights of Eucalyptol (1,8-Cineole) as an anti-arthritic agent: in vivo and in silico analysis of IL-17, IL-10, NF-κB, 5-LOX and COX-2.

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real-time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1ß and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1ß. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity.

ß-Citronellol: a potential anti-inflammatory and gastro-protective agent-mechanistic insights into its modulatory effects on COX-II, 5-LOX, eNOS, and ICAM-1 pathways through in vitro, in vivo, in silico, and network pharmacology studies.

BACKGROUND: The current study aimed to evaluate the anti-inflammatory, anti-oxidant, and pronounced gastro-protective activities of ß- Citronellol using in vitro, in vivo assays and in silico approaches. METHODS: In vitro assays, denaturation of bovine serum albumin, egg protein, and human Red Blood Cells (RBCs) membrane stabilization were performed, using Piroxicam as standard. For in vivo assessment, Histamine (0.1 ml from 1% w/v) and Formaldehyde (0.1 ml from 2% v/v) were used to mediate inflammation. In silico molecular docking and network pharmacology were employed to probe the possible target genes mediating gastroprotective effect of ß-Citronellol at 25, 50, and 100 mg/kg, using indomethacin-induced (25 mg/kg i.p) gastric ulcer in rats. Moreover, Gastric tissues were evaluated for morphological, histopathological, and bio-chemical analysis of PGE2, COX-I, COX-II, 5-LOX, eNOS, ICAM-1, oxygen-free radical scavengers (SOD, CAT), and oxidative stress marker (MDA). RESULTS: ß-Citronellol prevented denaturation of proteins and RBCs membrane stabilization with maximum effect observed at 6,400 µg/mL. Citronellol decreased rat's paw edema. Network pharmacology and docking studies revealed gastro-protective potential of Citronellol possibly mediated through arachidonic acid pathways by targeting COX-I, COX-II, PGE2, and 5-LOX. Citronellol reduced the ulcer indices, and histopathological changes. Further, ß-Citronellol (50 and 100 mg/kg) increased gastric PGE2, COX-1, and eNOS; while suppressing COX-2, 5-LOX and ICAM-1. Citronellol markedly enhanced the oxidative balance in isolated rat stomach tissues. CONCLUSIONS: The anti-inflammatory, anti-oxidant, and gastro-protective effects of ß-Citronellol against indomethacin-induced gastric ulcer model in rats through mediating COX-I, COX-II, PGE2, 5-LOX, eNOS, and ICAM-1 inflammatory markers.

Role of medicinal herbs and phytochemicals in post burn management.

Burn management is a natural and distinctly programmed process involving overlapping phases of hemostasis, inflammation, proliferation and remodeling. Burn wound healing involves initiation of inflammation, re-epithelialization, granulation, neovascularization and wound contraction. Despite the availability of multiple preparations for management of burn wound, there is dire need for efficacious alternative agents. Current approaches for burn wound management include pharmaceutical agents and antibiotics. However, high cost of synthetic drugs and accelerated resistance to antibiotics is challenging for both developed and developing nations. Among alternative options, medicinal plants have been a biocompatible, safe and affordable source of preventive/curative approaches. Due to cultural acceptance and patient compliance, there has been a focus on the use of botanical drugs and phytochemicals for burn wound healing. Keeping in consideration of medicinal herbs and phytochemicals as suitable therapeutic/adjuvant agents for burn wound management, this review highlights therapeutic potential of 35 medicinal herbs and 10 phytochemicals. Among these, Elaeis guineensis, Ephedra ciliate and Terminalia avicennioides showed better burn wound healing potential with varied mechanisms such as modulation of TNF-alpha, inflammatory cytokines, nitric oxide, eicosanoids, ROS and leukocyte response. Phytochemicals (oleanolic acid, ursolic acid, kirenol) also showed promising role in burn wound management though various pathways involving such as down regulation of TNF-alpha, IL-6 and inflammatory mediators including plasma proteases and arachidonic acid metabolites. This review provides a pavement for therapeutic/adjuvant use of potential botanical drugs and novel druggable phyto-compounds to target skin burn injury with diverse mechanisms, affordability and safety profile.

Bromocriptine therapy: Review of mechanism of action, safety and tolerability.

Bromocriptine is a sympatholytic dopamine D2 receptor agonist with remarkable bioactivities. It has been used clinically as a prescription drug for more than 30 years to treat hyperprolactinemia associated conditions, Parkinson's disease, acromegaly, prolactinomas and other pituitary hormone dependent adenomas and recently, diabetes mellitus as well as various other disorders. Long-term treatment with bromocriptine has minimal or no harmful effects on renal, hepatic, cardiac or hematologic functions. This review article was planned to study the hypothetical and proposed mechanism of action as well as provide a brief discussion about its safety issues and tolerability. Bromocriptine represents an attractive option with high efficacy and safety profile for hyperprolactinemia-associated conditions, acromegaly, parkinsonism, type 2 diabetes mellitus and various other diseases in a variety of dosage forms for best possible beneficial effects. It appeared to be an effective and safe addition to the pharmacopoeia of drugs for the treatment of a vast variety of diseases as monotherapy or in combination with other drugs.

Promising role of polymeric nanoparticles in the treatment of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory illness caused by an autoimmune disorder of synovial membrane resulting in synovial membrane dysfunction. The available treatment particularly focuses on inhibiting macrophage proliferation and reducing the generation of pro-inflammatory cytokines. However, therapeutic success of current treatment options at targeted site is limited; therefore, development of promising therapeutic strategy is the need of time that may provide better targeted delivery of drug with added safety. In development of precision medicine to manage RA, nanotechnology is a viable option to be considered. Recent research using nanoparticles for the treatment of RA, particularly polymeric nanoparticles, has been discussed in this article. Using polymeric nanoparticles as a therapeutic method has shown considerable promise of enhancing treatment success over standard medications used in routine. It is exclusively evident that the viability of using nanoparticles is mainly owed due to their biocompatibility, chemical stability, controlled drug release, and selective drug delivery to inflamed tissues in RA model animals. The current analysis focuses on the critical design characteristics of RA-targeted nanotechnology-based strategies in quest of better therapeutic strategies for RA, and to identify leading polymer as the most effective medications in RA therapy.

A flavonoid driven phyto-pharmacological effects of Capparis decidua Edgew. in rodents.

This study elicits the underlying mechanism(s) of Capparis decidua when used for different gut disorders. HPLC chromatogram of C. decidua extract (CD.Cr) and its respective fractions showed a variety of phytochemicals of which, kaempferol being in a high proportion. In mice, CD.Cr at doses of 70 and 150 mg/kg enhanced the wet feces output to 33 and 44% respectively as compared to carbachol (47.6%), while doses of 500 and 700 mg/kg, presented 41 and 70% safety against castor oil-driven diarrhea, respectively. Its flavonoid constituent, kaempferol at doses of (50 and 100 mg/kg) produced 51.7 and 82% safety when compared to nifedipine which provided 95% safety at dose of 40 mg/kg against castor oil-driven diarrhea like loperamide. In isolated jejunum preparations, C. decidua extract and its respective fractions (except pet-ether) produced atropine-sensitive inhibitory effects, whereas kaempferol and nifedipine showed atropine insensitive effects. Against high K+-induced contractions, C. decidua's fractions and kaempferol both exhibited a concentration-related non-specific inhibition while displacing the Ca++ -CRCs to right-ward with suppression in maximal response like nifedipine. In isolated rat ileal preparations, CD.Cr and respective fractions elicited atropine-sensitive gut excitatory responses. In summary, this article reports C. decidua's laxative effect through cholinergic receptor activation as well as its antidiarrheal effects, where its flavonoid constituent kaempferol produces Ca++ antagonist like activity, thus justifying C. decidua folk use in constipation and diarrhea.

Evaluation of prokinetic and laxative effects of Hippophae rhamnoides in rodents.

Hippophae rhamnoides (Family; Elaeagnaceae) fruit extract was investigated for prokinetic and gut excitatory effects to rationalize its therapeutic utility in gastrointestinal complaints like delayed gastric emptying and constipation. The fruit extract of Hippophae rhamnoides (Hr.Cr) prepared in hydro-methanol (30:70) was verified for flavonoids, tannins, coumarins and terpenes as plant constituents. In mice, Hr.Cr administration caused an increased in faecal production and charcoal meal transport (50-300mg/kg, per-oral.), similar to activity pattern of carbamylcholine (1 mg/kg). Laxative and prokinetic effects of Hr.Cr were found partially atropine-sensitive. On challenge with isolated intestinal tissues, Hr.Cr charged a dose-dependent spasmogenic effect on jejunum (0.01-1mg/mL) preparations of rabbit and in ileal tissues (guinea-pig) at the dose range of 0.03 to 3mg/mL, following predominant relaxing impact at increased concentrations. Unlike carbamylcholine, stimulant effect of Hr.Cr was partly antagonized in atropine incubated tissues. These data attest the laxative, prokinetic and gut excitatory activities of Hippophae rhamnoides probably mediated through partial activation of muscarinic receptors. Further in agreement of the current findings with earlier reports on gastric emptying effects of Hippophae rhamnoides seed oil, this is the first study of its kind providing insight into mechanism to the laxative potential of Hippophae rhamnoides fruit, thus rationalizing its medicinal use in constipation.

Pharmacological basis for the medicinal use of Alcea rosea in airways disorders and chemical characterization of its fixed oils through GC-MS.

Alcea rosea L. also known as Althea rosea belongs to the Malvaceae family. This medicinal herb, traditionally used to treat several conditions including airway disorders like asthma and chronic bronchitis. This study evaluated the bronchodilatory effects and possible mechanism of A. rosea on guinea-pig tracheal tissues. Moreover lipophilic profiling of A. rosea has been carried out by using Gas-Chromatography-Mass-Spectrometry. A total of 19 compounds have been identified from the plant, n-hexane fraction. These compounds have been further confirmed from their Van den Dool and Kratz (I) Indices. Major class of metabolite identified from the plant includes fatty acid, saturated and unsaturated fatty acid esters. Hydrocarbons have also been detected from the n-hexane fraction. These fatty acid esters have not been reported previously by GC-MS and were identified first time from the flowers of Alcea rosea. In-vitro experiments were performed on guinea-pig tracheal tissues, mounted in Kreb's solution at 37°C and bubbled with carbogen. In isolated guinea-pig trachea, A. rosea inhibited carbamylcholine and K+ (80 mM)-induced contractions, potentiated isoprenaline concentration-response curves (CRCs) and suppressed Ca2+ CRCs. These results suggest that A. rosea cause bronchodilation through dual inhibition of phosphodiesterase enzyme and Ca2+ influx, which substantiate its potential in airways disorders.

Faculty Development Initiatives: A prerequisite for capacity building and enhanced productivity in a medical institution.

OBJECTIVE: To determine the contribution of teaching, learning and assessment forum's initiatives on professional development of faculty and staff. METHODS: This retrospective study was conducted at the Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, from July to December 2016, and comprised teaching, learning and assessment activities carried out from 2012 to 2015. The responses acquired from feedback evaluation were recorded at the end of activity on a Likert-type scale ranging from 1-5. Positive responses were presented for each variable with respective activity type across the study years. The association of the effectiveness of teaching, learning and assessment between type of event and yearly outcome was also assessed. RESULTS: A total of 66activities were held during the study period. Of them, 49(74.24%) were workshops/human resource trainings, 5(7.57%) were courses and 12(18.18%) were seminars. Together, they involved over 500 participants. Objectives, disclosure statement, contents, level of interaction, acquired knowledge, time management, queries responded, organisational activity, course material and overall assessment showed consistent positive response across the years, but the acquisition of new knowledge differed significantly (p<0.05) through the study years. CONCLUSIONS: Teaching, learning and assessment initiatives, play a positive role in professional development of faculty and staff.

Pharmacological basis for the medicinal use of polyherbal formulation and its ingredients in cardiovascular disorders using rodents.

BACKGROUND: A compound herbal formulation (POL4) has been used in the indigenous system of medicine to treat cardiometabolic disorders like diabetes and associated hypertension. POL4 and most of its constituents have not been studied widely for its therapeutic use in hypertension. This study is aimed to determine the efficacy and possible insight into mechanism(s) for the medicinal use of POL4 and its ingredients in hypertension. METHODS: The aqueous methanolic extracts of POL4 (POL4.Cr) and its components [Cichorium intybus (Ci.Cr), Gymnema sylvestre (Gs.Cr), Nigella sativa (Ns.Cr) and Trigonella foenum graecum (Tfg.Cr)] were tested for blood pressure lowering activity in anaesthetized Sprague-Dawley rats. To assess the vasomodulatory effect, isolated tissue experiments were performed on rat aortic strips using isometric force transducer coupled with PowerLab data acquisition system. RESULTS: Administration of POL4 to rats caused a dose-dependent (1-100 mg/kg) fall in mean arterial pressure (MAP) with maximum effect of 85.33 ± 1.76% at 100 mg/kg, similar to the effect of verapamil. All ingredients of POL4 also decreased blood pressure with varying efficacy in following order Ns.Cr ≅ Ci.Cr > Tfg.Cr > Gs.Cr. In rat aortic preparations, POL4 and its ingredients inhibited K+ (80 mM)-induced contractions, Ci.Cr was the most potent followed by Ns.Cr > Tfg.Cr > Gs.Cr ≅ POL4. Against phenylephrine (P.E) contractions, Ci.Cr and Tfg.Cr exhibited complete relaxation, while POL4.Cr, Gs.Cr and Ns.Cr showed vasomodulatory effect. The Ca++ antagonist activity was confirmed when POL4 and its ingredients shifted Ca++ concentrations-response curves to the right in a manner similar to that of verapamil. On baseline of rat aorta, the parent formulation and its ingredients (except Tfg.Cr) exhibited partially phentolamine (1 µM)-sensitive vasoconstriction. CONCLUSION: These data show that POL4 and its constituents possess blood pressure lowering activity mediated through inhibition of Ca++ influx via membranous Ca++ channels and receptor (α-adrenergic) operated pathways. Thus, this study provides a rationale to the medicinal use of POL4 and its constituents in hypertension.

Studies on antihyperlipidemic and endothelium modulatory activities of polyherbal formulation (POL4) and its ingredients in high fat diet-fed rats.

A compound herbal formulation (POL4) is used traditionally in interior parts (Distt. Badin) of Sindh, Pakistan, for the treatment of metabolic disorders like diabetes and hyperlipidemia. This study is aimed to determine the effectiveness of POL4 and its ingredients in hyperlipidemia and associated endothelial dysfunction and hypertension. POL4 is composed of equal proportion of Nigella sativa, Cichorium intybus, Trigonella foenum graecum and Gymnema sylvestre mixed in powdered form. Chronic (6 to 7 weeks) administration of POL4 and its ingredients mixed in diet caused a notable attenuation in total cholesterol, low density lipoprotein cholesterol, triglycerides, atherogenic index, C-reactive protein and glucose, while it has increased high density lipoprotein levels. POL4 intervention markedly (p<0.01) reduced systolic blood pressure in rats to 127±1.92 vs. 145.4±1.07 mm of Hg using tail-cuff method and significantly (p<0.05) improved endothelium-dependent relaxation (75±2.88 vs. 82.75±1.22%) to acetylcholine in isolated aortae of rats in treatment groups using force transducer and PowerLab system. Similar activities were assessed on the part of ingredients of POL4. These findings indicate that POL4 and its ingredients possess antihyperlipidemic, endothelium-dependent modulatory and antihypertensive activities, thus providing an evidence to the vernacular use of POL4 in hyperlipidemia and hypertension.

The Prokinetic, Laxative, and Antidiarrheal Effects of Morus nigra: Possible Muscarinic, Ca(2+) Channel Blocking, and Antimuscarinic Mechanisms.

Morus nigra Linn. (black mulberry) is used in gastrointestinal ailments. This study demonstrates gut modulatory properties of M. nigra. The prokinetic, laxative, and antidiarrheal activities of M. nigra were assessed in mice, while isolated rabbit jejunum and guinea-pig ileum were used to explore insight into mechanism(s). At 30 and 70 mg/kg, the crude extract of M. nigra (Mn.Cr) exhibited atropine-sensitive prokinetic and laxative effects, similar to carbachol (CCh). While at higher doses (100, 300, and 500 mg/kg), Mn.Cr offered protection against castor oil-induced diarrhea. In rabbit jejunum, Mn.Cr and its chloroform fraction inhibited CCh-induced contractions more potently compared with high K(+) (80 mm). Conversely, petroleum fraction was more potent against high-K(+) -induced contractions. At 0.01 mg/mL, Mn.Cr caused a parallel shift in acetylcholine concentration-response curves (CRCs) followed by a non-parallel shift at 0.03 mg/mL, similar to dicyclomine. At further tested concentrations, Mn.Cr (0.1 and 0.3 mg/mL) and petroleum fraction suppressed Ca(2+) CRCs, similar to verapamil. In guinea-pig ileum, Mn.Cr, its aqueous and ethyl acetate fractions exhibited atropine-sensitive gut stimulant activity along with additional uncharacterized excitatory response in the aqueous fraction only. These results suggest that black mulberry possesses prokinetic, laxative, and antidiarrheal effects, putatively mediated through cholinomimetic, antimuscarinic, and Ca(2+) antagonist mechanisms, respectively. Copyright © 2016 John Wiley & Sons, Ltd.

Antispasmodic and antidiarrheal activities of rhizomes of Polygonatum verticillatum maneuvered predominately through activation of K⁺ channels: Components identification through TLC.

Polygonatum verticillatum has traditionally been used for various purposes. The present study was aimed to validate the antispasmodic and antidiarrheal properties of crude methanolic extract of rhizomes of P. verticillatum (PR). Isolated rabbit jejunum preparations were suspended in tissue baths to measure the isotonic responses using Power Lab data acquisition system for the antispasmodic activity of PR, while the antidiarrheal activity was conducted in vivo in mice. PR caused complete relaxation of the spontaneous contractions of isolated rabbit jejunum preparations in a dose-dependent mode. A complete inhibition was observed against low potassium (K(+); 25 mM)-induced contractions, while the plant extract partially inhibited the high K(+)(80 mM)-induced contractions. From a mechanistic point of view, the spasmolytic effect of PR against low K(+)was antagonized by glibenclamide similar to the effect of cromakalim, thus showing the presence of constituents in PR mediating spasmolytic activity predominantly through the activation of adenosine triphosphate-sensitive K(+)channels. When tested against castor oil-induced diarrhea in mice, oral administration of the plant extract manifested marked antidiarrheal activity at the doses of 500 and 1000 mg/kg similar to loperamide. This study provided a pharmacological basis for the medicinal use of PR in abdominal colic and diarrhea.

Coadministration of black seeds and turmeric shows enhanced efficacy in preventing metabolic syndrome in fructose-fed rats.

Among noncommunicable diseases, metabolic syndrome (MS), a cluster of metabolic disorders including obesity, hyperglycemia, hyperlipidemia and hypertension, is highly prevalent in modern society. Its management requires lifestyle modifications and/or the life-long use of multiple medications, hence demanding development of safe alternative remedies. This study was aimed to establish the efficacy of combined use of black seeds and turmeric using fructose-fed rat model of MS. The high-performance liquid chromatographic fingerprints of turmeric and black seeds showed the presence of curcumin and thymoquinone, respectively, as their major constitutes. Different doses of black seeds and turmeric, individually and in combination, were administered to fructose-fed rats for up to 6 weeks representing characteristic features of MS. At 3 weeks of the treatment, black seeds and turmeric lowered (P < 0.01) high blood pressure and low-density lipoprotein cholesterol, respectively, whereas their coadministration reduced (P < 0.01) both high blood pressure and hypertriglyceridemia. At 6 weeks, the coadministration of both herbs, at half the doses of individual herbs, was the most effective (P < 0.001) in preventing hypertension, hyperglycemia, dyslipidemia, hyperinsulinemia, and endothelial dysfunction than the individual herbs. This study demonstrates the therapeutic superiority of the combination of black seeds and turmeric at low doses over individually tested herbs, in improving features of MS.

Antidiarrhoeal, antisecretory and antispasmodic activities of Matricaria chamomilla are mediated predominantly through K(+)-channels activation.

BACKGROUND: Matricaria chamomilla commonly known as "Chamomile" (Asteraceae) is a popular medicinal herb widely used in indigenous system of medicine for a variety of ailments. However, there is no detailed study available showing its effectiveness in hyperactive gut disorders like, abdominal colic and diarrhoea. This study was designed to determine the pharmacological basis for the folkloric use of Matricaria chamomilla in diarrhoea. METHODS: The crude aqueous-methanolic extract of Matricaria chamomilla (Mc.Cr) was studied for its protective effect in mice against castor oil-induced diarrhoea and intestinal fluid accumulation. The isolated rabbit jejunum was selected for the in-vitro experiments using tissue bath assembly coupled with PowerLab data acquisition system. RESULTS: Oral administration of Mc.Cr to mice at 150 and 300 mg/kg showed marked antidiarrhoeal and antisecretory effects against castor oil-induced diarrhoea and intestinal fluid accumulation, simultaneously, similar to the effects of cromakalim and loperamide. These effects of plant extract were attenuated in animals pretreated with K(+) channel antagonist, glibenclamide (GB) or 4-aminopyridine (4-AP). When tested in isolated rabbit jejunum, Mc.Cr caused a dose-dependent (0.3-3 mg/ml) relaxation of spontaneous and low K(+) (25 mM)-induced contractions, while it exhibited weak inhibitory effect on high K(+) (80 mM). The inhibitory effect of Mc.Cr on low K(+)-induced contractions was partially inhibited in the presence of GB, while completely blocked by 4-AP. Cromakalim, an ATP-sensitive K(+) channel opener, caused complete relaxation of low K(+)-induced contractions with little effect on high K(+). Pretreatment of tissues with GB blocked the inhibitory effects of cromakalim on low K(+), while the presence of 4-AP did not alter the original effect. Verapamil, a Ca(++) channel antagonist, caused complete relaxation of both low and high K(+)-induced contractions with similar potency. The inhibitory effect of verapamil was insensitive to GB or 4-AP. When assessed for Ca(++) antagonist like activity, Mc.Cr at high concentrations caused rightward shift in the Ca(++) concentration-response curves with suppression of the maximum response, similar to the effect of verapamil, while cromakalim did not show similar effect. CONCLUSIONS: This study indicates that Matricaria chamomilla possesses antidiarrhoeal, antisecretory and antispasmodic activities mediated predominantly through K(+)-channels activation along with weak Ca(++) antagonist effect.

Studies on two polyherbal formulations (ZPTO and ZTO) for comparison of their antidyslipidemic, antihypertensive and endothelial modulating activities.

BACKGROUND: Cardiovascular disorders (CVDs) are the leading cause of disease burden worldwide. Apart from available synthetic drugs used in CVDs, there are many herbal formulations including POL-10 (containing 10 herbs), which have been shown to be effective in animal studies but POL-10 was found to cause tachycardia in rodents as its side effect. This study was designed to modify the composition of POL-10 for better efficacy and/or safety profile in CVDs. METHODS: To assess the antidyslipidemic, antihypertensive and endothelial modulatory properties of two herbal formulations, (ZPTO and ZTO) containing Z: Zingiber officinalis, P: Piper nigrum, T: Terminalia belerica and O: Orchis mascula, different animal models including, tyloxapol and high fat diet-induced dyslipidemia and spontaneously hypertensive rats (SHR) were used. Effect on endothelial function was studied using isolated tissue bath set up coupled with PowerLab data acquisition system. The antioxidant activity was carried out using DPPH radical-scavenging assay. RESULTS: Based on preliminary screening of the ingredients of POL-10 in tyloxapol-induced hyperlipidemic rats, ZPTO and ZTO containing four active ingredients namely; Z, P, T and O were identified for further studies and comparison. In tyloxapol-induced hyperlipidemic rats, both ZPTO and ZTO caused significant reduction in serum triglyceride (TG) and total cholesterol (TC). In high fat diet-fed rats, ZPTO decreased TC, low-density lipoproteins cholesterol (LDL-C) and atherogenic index (AI). ZTO also showed similar effects to those of ZPTO with additional merits being more effective in reducing AI, body weight and more importantly raising high-density lipoproteins. In SHR, both formulations markedly reduced systolic blood pressure, AI and TG levels, ZTO being more potent in reversing endothelial dysfunction while was devoid of cardiac stimulatory effect. In addition, ZTO also reduced LDL-C and improved glucose levels in SHR. In DPPH radical-scavenging activity test, ZTO was also more potent than ZPTO. CONCLUSION: The modified formulation, ZTO was not only found more effective in correcting cardiovascular abnormalities than ZPTO or POL-10 but also it was free from tachycardiac side-effect, which might be observed because of the presence of Piper nigrum in ZPTO.

Studies on tracheorelaxant and anti-inflammatory activities of rhizomes of Polygonatum verticillatum.

BACKGROUND: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders. METHODS: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the lipoxygenase inhibitory activity was performed in the in-vitro assay. Various chromatographic and spectroscopic techniques were used for the isolation and characterization of pure molecules. RESULTS: In isolated guinea-pig tracheal preparations, PR caused complete inhibition of the high K+ (80 mM) and carbachol-induced contractions however, it was more potent against K+ than CCh, similar to verapamil. Pretreatment of the tissue with PR, displaced the Ca2+ concentration-response curves to the right, similar to that induced by verapamil, indicating the presence of Ca2+ channel blocking like activity. When tested on carrageenan-induced rat paw edema, PR demonstrated a marked reduction in edema with 65.22% protection at 200 mg/kg, similar to aspirin. In the in-vitro assay, PR showed lipoxygenase inhibitory activity (IC50: 102 ± 0.19 µg/mL), similar to baicalein. Bioactivity-guided fractionation led to the isolation of 2-hydroxybenzoic acid and ß-sitosterol. CONCLUSIONS: These results indicate that the plant possesses tracheorelaxant, mediated possibly through a Ca2+ channel blockade mechanism, and anti-inflammatory activities, which may explain the medicinal use of this plant in airway disorders and inflammation.

Studies on prokinetic, laxative and spasmodic activities of Phyllanthus emblica in experimental animals.

This study was aimed to provide pharmacological basis for the medicinal use of Phyllanthus emblica fruit in indigestion and constipation using the in-vivo and in-vitro assays. The crude extract of the dried fruits of Phyllanthus emblica (Pe.Cr) and its fractions were tested positive for alkaloids, saponins, tannins, terpenes, flavonoids, sterols and coumarins. Pe.Cr at the doses of 100 and 300 mg/kg exhibited the prokinetic and laxative activities in mice, which were found partially sensitive to atropine. In isolated guinea-pig ileum and rabbit jejunum, the crude extract and its aqueous fraction (Pe.Aq) caused concentration-dependent and partially atropine-sensitive stimulatory effects followed by relaxation at higher tested concentrations, being more efficacious in guinea pig, while more potent in rabbit tissues. The petroleum fraction (0.003-0.1 mg/mL) exhibited fully atropine-sensitive contractions in both guinea-pig and rabbit tissues. However, the ethyl acetate and chloroform fractions (0.003-1.0 mg/mL) showed only spasmolytic activity when studied in spontaneously contracting rabbit jejunum. This study showed that the Phyllanthus emblica possesses prokinetic and laxative activities in mice along with spasmodic effect in the isolated tissues of guinea pig and rabbit, mediated partially through activation of muscarinic receptors; thus, this study provides a rationale for the medicinal use of Phyllanthus emblica fruits in indigestion and constipation.