Pharmacokinetics-Based Optimization of Phototherapy in Neonates Undergoing Treatment for Hyperbilirubinemia.

Introduction: Neonatal jaundice results from combined effects of both increased production of bilirubin and decreased hepatic excretory capacity in neonates. Since its discovery, phototherapy is the most widespread treatment used in neonatal jaundice. In this work, we try to search for a relationship between exposure to phototherapy and decrease in serum bilirubin (linearity vs proportionality). Methods:The present research was non-randomized prospective study conducted in the Neonatal Intensive Care Unit (NICU), Department of Paediatrics, AIIMS, New Delhi, and the Department of Pharmacology, AIIMS, New Delhi, India. Subjects were recruited from neonates admitted in NICU AIIMS, which meets our selection criteria. Infants were given a low dose of either phototherapy continuously or phototherapy for the first six hours and a double dose of phototherapy for the next six hours. Samples were collected before the beginning of the study (0 hours) and then at six and 12 hours. Bilirubin concentration was measured using HPLC and (LC-MS/MS). Results and conclusion:The percentage of reduction during the 6-12-hour interval was compared with that during the 0-6-hour interval if all experimental conditions were kept unchanged. A relationship curve between percentage of reduction and irradiance was created based on the percentage of reduction in serum bilirubin during the 0-6-hour and 0-12-hour intervals. The present study suggests that the relationship between efficacy, as measured by percentage of reduction in serum bilirubin, and irradiance is unlikely to be linear. Collected data are insufficient to clearly distinguish between proportionality and saturation point, considering that the results may be possible with both of these hypotheses.

Bacosides enrichment does not improve the anti-amnesic effect of Bacopa monnieri: behavioural and biochemical evidences.

Bacopa monnieri (L.) Wettst. (BM) has been traditionally used in Ayurveda for improving memory and cognitive deficits which is also evidenced through experimental and clinical studies. The neuropharmacological properties of BM are attributed to "bacosides", a complex mixture of saponin compounds. BM extracts enriched with bacosides offers commercial advantage due to perceived higher efficacy. However, there is no scientific data to support the same. In the present study, methanolic extract of BM (BME) was compared with bacosides enriched (BME-EF) vis a vis bacosides free fraction (BME-FF). Potential antioxidant and cholinesterase inhibitory activity has been evaluated using in vitro and in vivo methods. BME showed not only the highest anti-amnesic efficacy but also antioxidant and cholinesterase inhibitory activity, followed by either BME-FF or BME-EF. Interestingly, no significant differences were found in between the groups. These findings dispel the notion that bacosides enrichment enhances anti-amnesic efficacy and also suggests the contribution of other components.

In vivo anti-arthritic activity of Bauhinia purpurea Linn. Bark Extract.

OBJECTIVE: Bauhinia purpurea (BP) Linn. (Caesalpiniaceae) is a plant of great medicinal importance and has been used since ancient times for treating many inflammatory conditions including arthritis. This study investigates the anti-arthritic potential of the hydroalcoholic extract from the stem bark of BP. MATERIALS AND METHODS: The anti-inflammatory and anti-arthritic activity of BP at various doses was used to evaluate its anti-inflammatory activity and anti-arthritic activity. Serum of arthritic rats was collected at day 21 for detecting serum cytokines level and to evaluate the effect of BP on its serum level. Furthermore, the safety of BP was evaluated in acute (5 days) and subacute (28 days) toxicity study in rats. RESULTS: There was a significant inhibition (P < 0.01) in paw edema at a different time scale with different doses of BP (50, 100, and 200 mg/kg). BP also demonstrated dose-dependent anti-arthritic activity on all observation days (3, 7, 14, and 21). In addition, there was also a significant decrease (P < 0.01) in oxidative stress markers, circulating pro-inflammatory cytokine (tumor necrosis factor alpha from 45.91 to 37.44, interleukin-1 (IL-1) ß from 18.24 to 16.06, and IL-6 from 69.77 to 58.44) and an increase in anti-inflammatory cytokine (IL-10 from 8.07 to 12.07) levels. BP was found to be safe with an oral LD50 value of >2 g/kg in acute toxicity study and also no toxicological effect was observed in the oral subacute toxicity study. CONCLUSION: This study demonstrates that BP bark possesses anti-arthritic activity potential and confirm its folklore use in the treatment of inflammatory conditions.

Comparison of three different extracts of Centella asiatica for anti-amnesic, antioxidant and anticholinergic activities: in vitro and in vivo study.

Centella asiatica (CA) has been used by Ayurvedic medical practitioners in India for almost 3000 years. The neuropharmacological properties of CA and its constituents have been studied extensively. Anti-oxidant, free radical scavenging and cholinergic modulatory activities are the reported mechanisms of action for its efficacy in memory disorders. Its medicinal values are mainly attributed to the presence of several triterpenes, namely asiatic acid, madecassic acid, asiaticoside, and madecassoside. The present study was aimed to investigate the role of these triterpenes content in CA extract on the antioxidant, cholinesterase modulation and anti-amnesic properties. The fractions of CA extract enriched for (CAE-EF) and depleted/freed of (CAE-FF) triterpenes contents were compared with methanolic extract (CAE). Both in vitro and in vivo methods for evaluation of antioxidant and anticholinergic activities were used. In vitro, free radical scavenging assays (ABTS, DPPH, NO, NORAC, and ORAC) and cholinesterase (AChE and BuChE) inhibition assays were used. For evaluation of anti-amnesic effect, scopolamine induced amnesia in rats, as the acute model of memory loss was used. Following behavioural assessments (MWM, PA, EPM), biomarkers of oxidative stress (reduced GSH, MDA and SOD activity) and cholinesterase (AChE and BuChE) status were also estimated in cerebral cortex and hippocampus of rat brain. The methanolic extract (CAE) was found to perform best among all three fractions for in vitro free radical scavenging, cholinesterase inhibition, improvement of scopolamine-induced amnesia and also in vivo antioxidant effect and cholinesterase inhibitory activities. Interestingly triterpenes free fraction (CAE-FF) showed better antioxidant activity than triterpenes enriched fraction (CAE-EF) along with comparable anti-amnesic effect. This indicates that triterpenes are not solely responsible for antioxidant activity, cholinesterase inhibitory and anti-amnesic effect of CA.

Advances in Carbon Nanotubes-Hydrogel Hybrids in Nanomedicine for Therapeutics.

In spite of significant advancement in hydrogel technology, low mechanical strength and lack of electrical conductivity have limited their next-level biomedical applications for skeletal muscles, cardiac and neural cells. Host-guest chemistry based hybrid nanocomposites systems have gained attention as they completely overcome these pitfalls and generate bioscaffolds with tunable electrical and mechanical characteristics. In recent years, carbon nanotube (CNT)-based hybrid hydrogels have emerged as innovative candidates with diverse applications in regenerative medicines, tissue engineering, drug delivery devices, implantable devices, biosensing, and biorobotics. This article is an attempt to recapitulate the advancement in synthesis and characterization of hybrid hydrogels and provide deep insights toward their functioning and success as biomedical devices. The improved comparative performance and biocompatibility of CNT-hydrogels hybrids systems developed for targeted biomedical applications are addressed here. Recent updates toward diverse applications and limitations of CNT hybrid hydrogels is the strength of the review. This will provide a holistic approach toward understanding of CNT-based hydrogels and their applications in nanotheranostics.

Protective effect of Terminalia chebula against seizures, seizure-induced cognitive impairment and oxidative stress in experimental models of seizures in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Teminalia chebula (TC) has been traditionally used in the Ayurvedic system of medicine primarily for gastrointestinal disorders. Its fruit extract has also been used to treat epilepsy and other CNS disorders. AIM OF THE STUDY: To evaluate the effect of hydroalcoholic fruit extract of Terminalia chebula (HETC) on experimental models of seizures, seizure-induced cognitive impairment and oxidative stress in rats. MATERIALS AND METHODS: In vitro antioxidant activity of HETC was evaluated by using ABTS, NO and DPPH radical scavenging assay. For in-vivo study, seizures were induced in Wistar rats (200-225g) by pentylenetetrazole (PTZ) and maximal-electroshock. (MES). The anticonvulsant effect of the HETC (250, 500, and 1000mg/kg, orally) was evaluated in seizure models. The therapeutic and sub-therapeutic dose of valproate and phenytoin were also assayed. The potential effect of co-administration of HETC (500mg/kg) with sub-therapeutic dose of valproate and phenytoin were also evaluated in PTZ and MES seizures model respectively. Effect on cognition was assessed using elevated plus maze (EPM) and passive avoidance test (PA). The in- vivo oxidative stress parameters (malondialdehyde and glutathione) were assessed in the cerebral cortex and hippocampus part of rat brain. RESULTS: The IC50 value of HETC in in vitro antioxidant assays i.e. ABTS, DPPH and NO radical scavenging assay was found to be 2.27µg/ml, 6.04µg/ml and 4.37µg/ml respectively. In experimental study, PTZ and MES treated groups exhibited 100% seizures with increased oxidative stress (p < 0.001) and cognitive deficits (p < 0.01) as compared to control group. HETC at highest dose (1000mg/kg) showed 83.33% (5/6) protection in MES induced seizures while 66.66% (4/6) protection in PTZ induced seizures. However, HETC (1000mg/kg) and co-administration of sub-therapeutic dose of HETC with valproate and phenytoin showed complete protection. In addition, it also attenuated the seizure induced oxidative stress and cognitive impairment as indicated by significant (p < 0.01) improvement in the transfer latencies in EPM and PA as compared to PTZ and MES treated group. CONCLUSIONS: The findings suggest that HETC exhibited significant anticonvulsant activity and also potentiated the subtherapeutic dose of phenytoin and valproate indicate its usefulness as an adjuvant to antiepileptic drugs with an advantage of preventing cognitive impairment and oxidative stress.

Safety assessment and attenuation of cisplatin induced nephrotoxicity by tuberous roots of Boerhaavia diffusa.

Cisplatin (Cis-diaminedichloroplatinum II) is a chemotherapeutic agent having well documented adverse effect as nephrotoxicity. This study was designed to evaluate the nephroprotective role of Boerhaavia diffusa in cisplatin-induced acute kidney injury. Wistar rats (n = 6) were allocated into six groups constituting normal control, cisplatin-induced, Boerhaavia diffusa root extract in doses 50, 100 and 200 mg/kg and Boerhaavia diffusa per se group, administered orally for a period of ten days. Intraperitoneal injection of cisplatin was administered on day 7, to all groups except normal control and Boerhaavia diffusa per se group. On day 10, cisplatin resulted in substantial nephrotoxicity in Wistar rats with significant (p < 0.001) elevation in serum creatinine and blood urea nitrogen, decline in the concentrations of reduced glutathione and superoxide dismutase, elevation in TNF-α level in renal tissues. Boerhaavia diffusa at a dose of 200 mg/kg body weight significantly (p < 0.001) ameliorates increased in serum creatinine, blood urea nitrogen, oxidative stress and inflammatory markers. In parallel to this, it also exhibits antiapoptotic activity through the reduction of active caspase-3 expression in kidneys. Findings indicate that Boerhaavia diffusa is effective in mitigating cisplatin-induced nephrotoxicity and thus, for this the acute and sub-acute toxicity studies conducted to evaluate the safety profile of Boerhaavia diffusa. The no-observed adverse effect level (NOAEL) of tuberous roots of Boerhaavia diffusa root extract was 1000 mg/kg.

Cissampelos pareira Linn: Natural Source of Potent Antiviral Activity against All Four Dengue Virus Serotypes.

BACKGROUND: Dengue, a mosquito-borne viral disease, poses a significant global public health risk. In tropical countries such as India where periodic dengue outbreaks can be correlated to the high prevalence of the mosquito vector, circulation of all four dengue viruses (DENVs) and the high population density, a drug for dengue is being increasingly recognized as an unmet public health need. METHODOLOGY/PRINCIPAL FINDINGS: Using the knowledge of traditional Indian medicine, Ayurveda, we developed a systematic bioassay-guided screening approach to explore the indigenous herbal bio-resource to identify plants with pan-DENV inhibitory activity. Our results show that the alcoholic extract of Cissampelos pariera Linn (Cipa extract) was a potent inhibitor of all four DENVs in cell-based assays, assessed in terms of viral NS1 antigen secretion using ELISA, as well as viral replication, based on plaque assays. Virus yield reduction assays showed that Cipa extract could decrease viral titers by an order of magnitude. The extract conferred statistically significant protection against DENV infection using the AG129 mouse model. A preliminary evaluation of the clinical relevance of Cipa extract showed that it had no adverse effects on platelet counts and RBC viability. In addition to inherent antipyretic activity in Wistar rats, it possessed the ability to down-regulate the production of TNF-α, a cytokine implicated in severe dengue disease. Importantly, it showed no evidence of toxicity in Wistar rats, when administered at doses as high as 2g/Kg body weight for up to 1 week. CONCLUSIONS/SIGNIFICANCE: Our findings above, taken in the context of the human safety of Cipa, based on its use in Indian traditional medicine, warrant further work to explore Cipa as a source for the development of an inexpensive herbal formulation for dengue therapy. This may be of practical relevance to a dengue-endemic resource-poor country such as India.

Panchagavya Ghrita, an Ayurvedic formulation attenuates seizures, cognitive impairment and oxidative stress in pentylenetetrazole induced seizures in rats.

Panchagavya Ghrita (PG), according to Ayurvedic formulary of India (AFI), is used to treat epilepsy (apasmara), fever (jvara), mania (unmade) and jaundice (kamala). In the present study, we examined its effect on convulsions, oxidative stress and cognitive impairment in pentylenetetrazole (PTZ) induced seizures in rats. PG @ 250, 500, 1000, 2000 and 4000 mg/kg was administered orally for 7 days to male Wistar rats. On day 7, PTZ (60 mg/kg) was injected intraperitoneally 2 h after the last dose of PG. Sodium valproate (300 mg/kg) was used as positive control. Latency to myoclonic jerks, clonus and generalized tonic clonic seizures (GTCS) were recorded for seizure severity. Cognitive impairment was assessed using elevated plus maze and passive avoidance tests. Malondialdehyde and reduced glutathione levels were measured in rat brain. The results have shown that pretreatment with PG @ 500, 1000, 2000 and 4000 mg/kg exhibited 16.6, 33.3, 50 and 100% protection against occurrence of GTCS. The pretreatment with PG has significantly improved cognitive functions and the oxidative stress induced by seizures demonstrating its protective effect against PTZ induced seizures, and further, use of PG as an anticonvulsant in Ayurvedic system of medicine.

Anti-inflammatory and antiarthritic activity of UNIM-301 (a polyherbal unani formulation) in Wistar rats.

BACKGROUND: UNIM-301 is a polyherbal formulation used in the Unani system of medicine for the treatment of joint pain and rheumatoid arthritis (RA). OBJECTIVE: The objective was to evaluate the anti-inflammatory and antiarthritic activity of UNIM-301 in carrageenan-induced paw edema and complete Freund's Adjuvant (CFA) induced arthritis. MATERIALS AND METHODS: The anti-inflammatory and antiarthritic activity of UNIM-301 was evaluated using carrageenan-induced paw edema and CFA induced animal arthritis models, respectively, in doses of 250, 500, and 1000 mg/kg body weight. Anti-inflammatory activity of UNIM-301 was evaluated using carrageenan-induced paw edema model using a digital plethysmometer. Anti-arthritic activity was evaluated using CFA induced arthritis, and joint sizes were measured at regular intervals using a micrometer screw gauge. Serum was collected and subjected to estimation of pro-inflammatory cytokine. Indomethacin 3 mg/kg body weight) was used as a standard drug in both the models. The acute and chronic toxicity study was carried out to evaluate the safety of the test drug. RESULTS: UNIM-301 treatment produced a dose-dependent reduction in paw edema and paw thickness in carrageenan-induced paw edema and CFA-induced arthritis, respectively, as compared to control. UNIM 301 also reduced the expression of pro-inflammatory mediator in a dose-dependent manner as compared to control. CONCLUSION: The result of the present study suggests that anti-inflammatory and anti-arthritic activity of UNIM-301, which might be accredited to inhibitory activity on pro-inflammatory cytokines to its various individual constituents.

Do herbal medicines have potential for managing snake bite envenomation?

Snake envenomation is a global public health problem, with highest incidence in Southeast Asia. Inadequate health services, difficult transportation and consequent delay in antisnake venom administration are the main reasons for high mortality. Adverse drug reactions and inadequate storage conditions limit the use of antisnake venom. The medicinal plants, available locally and used widely by traditional healers, therefore need attention. A wide array of plants and their active principles have been evaluated for pharmacological properties. However, numerous unexplored plants claimed to be antidotes in folklore medicine need to be studied. The present article reviews the current status of various medicinal plants for the management of snake bite.

Evaluation of disease modifying activity of Coriandrum sativum in experimental models.

BACKGROUND & OBJECTIVES: Coriandrum sativum (CS), has been widely used in traditional systems of medicine for treatment of rheumatoid arthritis. However, the mechanism of action for its antiarthritic effects is not clearly known. Therefore, the present study was carried out to evaluate the antiarthritic activity of CS in rats in two experimental models. METHODS: The antiarthritic activity of CS seed hydroalcoholic extract (CSHE) was evaluated in adult Wistar rats by using two experimental models, viz. formaldehyde and Complete Freund's adjuvant (CFA) induced arthritis. The expression of pro-inflammatory cytokines (predominantly contributed by macrophages) was also evaluated. TNF- α level was estimated in serum by ELISA method. TNF-R1, IL-1 ß and IL-6 expression in the synovium was analysed by immunohistochemistry. RESULTS: CSHE produced a dose dependent inhibition of joint swelling as compared to control animals in both, formaldehyde and CFA induced arthritis. Although there was a dose dependent increase in serum TNF-α levels in the CSHE treated groups as compared to control, the synovial expression of macrophage derived pro-inflammatory cytokines/cytokine receptor was found to be lower in the CSHE treated groups as compared to control. INTERPRETATION & CONCLUSIONS: Our results demonstrate that the antiarthritic activity of CSHE may be attributed to the modulation of pro-inflammatory cytokines in the synovium. In further studies CSHE could be explored to be developed as a disease modifying agent in the treatment of RA.

Safety evaluation of an Ayurvedic medicine, Arogyavardhini vati on brain, liver and kidney in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Arogyavardhini vati, an Ayurvedic polyherbal formulation has been used for liver and skin disorders in the Ayurvedic system of medicine. However, toxicity due to the presence of heavy metals in this traditional medicine is a matter of concern. AIM OF THE STUDY: To evaluate the safety of Arogyavardhini vati on brain, liver and kidney in rats. MATERIALS AND METHODS: Arogyavardhini vati at doses of 50, 250 and 500mg/kg (1, 5 and 10 times of human equivalent dose respectively), mercury chloride (1mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioral parameters were assessed on day 1, 7th, 14th and 28th using Morris water maze, passive avoidance, elevated plus maze and rota rod. Biochemical parameters (acetyl-cholinesterase activity, malondialdehyde, reduced glutathione), histopathology and mercury level in brain, liver, kidney were assessed at the end of the experiment. RESULTS: There was no significant change in behavioral parameters, acetyl-cholinesterase activity, liver function (ALT, AST, ALP and bilirubin) and kidney (serum urea and creatinine) function tests at all doses of Arogyavardhini vati (50, 250 and 500mg/kg) as compared to normal control. However, significant change was observed in mercury chloride treated group. Mercury chloride treated group as well as Arogyavardhini vati treated groups (50, 250 and 500mg/kg) showed increased levels of mercury in brain, liver and kidney as compared to normal control. Histopathological results showed significant cytoarchitectural changes in brain, liver and kidney architecture in mercury chloride treated group. Whereas, normal cytoarchitecture was observed at all doses of Arogyavardhini vati. CONCLUSION: The finding of the present study suggests that Arogyavardhini vati in the doses equivalent up to 10 times of the human dose administered to rats for 28 days does not have appreciable toxicological effects on brain, liver and kidney.

Linseed oil: an investigation of its antiarthritic activity in experimental models.

Food sources rich in omega-3 fatty acids have been valued for their beneficial effect in the management of inflammatory disorders. The present study evaluates the antiarthritic and immunomodulatory activity of Linum usitatissimum fixed oil (LUFO) in experimental models. The LUFO produced a dose-dependent reduction in joint swelling and circulating TNF-α levels in both preventive and curative protocols of arthritis induced by complete Freund's adjuvant (CFA). Expression of TNF-R1 and Interleukin (IL) 6 proteins in the arthritic paw was also significantly reduced in the LUFO-treated animals. In the cotton pellet induced granuloma model, LUFO treatment significantly reduced the dry granuloma weight as compared with the control group. Results of our present study thus demonstrate the antiarthritic and disease modifying activity of LUFO. We believe that dietary incorporation of LUFO may be beneficial in the prevention and management of rheumatoid arthritis and other chronic inflammatory disorders.

Investigation into the anti-inflammatory and antigranuloma activity of Colchicum luteum Baker in experimental models.

The present study evaluates the anti-inflammatory and antigranuloma activity of CLHE in experimental models, viz. carrageenan-induced paw edema, subcutaneous cotton pellet implantation-induced granuloma formation, and complete Freund's adjuvant-induced stimulation of peritoneal macrophages in rats. Serum TNF-alpha, IL-6, and IL-1 beta levels were estimated as markers for global effects of inflammation. TNF-R1 protein expression was estimated in stimulated peritoneal macrophages. There was a significant reduction (P < 0.05) of paw edema in the CLHE-treated groups as compared to control. In the cotton pellet-induced granuloma model, there was a significant (P < 0.05) reduction in the dry granuloma weight and serum TNF-alpha, IL-6, and IL-1beta levels in the CLHE-treated group as compared to control. Immunoblot analysis for TNF-R1 also demonstrated a significant reduction in the receptor protein expression on stimulated macrophages. Result of the present study thus demonstrates and validates the antigranuloma activity of CLHE.

Monitoring of mercury, arsenic, cadmium and lead in Ayurvedic formulations marketed in Delhi by flame AAS and confirmation by ICP-MS.

The quality and safety of Ayurvedic formulations has become a serious issue, as this Indian system of medicine is used by 80% of the Indian population. Hence, the present study was performed to evaluate heavy metals contents by flame atomic absorbance spectroscopy (AAS) measurements and confirmation by inductive coupled plasma-mass spectroscopy (ICP-MS). A total of 78 formulations (56 herbal, 19 herbometallic and 3 metallic) were sampled. In herbal formulations, lead in 19.6% (11/56), cadmium in 21.4% (12/56), mercury and arsenic in 5.3% (3/56) were above the limit. Lead in 52.6% (10/19) of samples, cadmium in 26.3% (5/19) and mercury and arsenic contained in one herbometallic sample was above the limit. Heavy metals in all metal formulations were above the WHO limit. Significant batch variation was observed. The analytical results of flame AAS and ICP-MS did not differ significantly in the range of measurements in this study, which proves that both methods are satisfactory for estimation of heavy metals in these type of samples.

Antiarthritic activity of majoon suranjan (a polyherbal Unani formulation) in rat.

BACKGROUND & OBJECTIVES: Majoon Suranjan (MS) is a polyherbal formulation used in Unani system of medicine for the treatment of rheumatoid arthritis (RA). The present study evaluates the antiarthritic efficacy of this formulation in three different experimental models. METHODS: The anti-inflammatory activity of MS (in doses of 450, 900 and 1800 mg/kg body wt) was evaluated using the turpentine oil induced paw oedema model and the antiarthritic efficacy was evaluated using the formaldehyde and complete Freund's adjuvant (CFA) induced arthritis models. Aspirin (100 mg/kg body wt) was used as the standard drug in all the models. In order to assess the safety of the test drug, oral acute and 28 day toxicity studies were also carried out. RESULTS: MS produced a dose dependent protective effect in all the experimental models. Its antiarthritic efficacy was comparable to aspirin in formaldehyde induced arthritis and was superior to aspirin in turpentine oil induced paw oedema and CFA induced arthritis. MS also inhibited the delayed increase in joint diameter as seen in control and aspirin treated animals in CFA induced arthritis. Oral LD 50 of MS was found to be >5000 mg/kg in rats. Chronic administration did not produce any significant physiological changes in the tested animals. INTERPRETATION & CONCLUSIONS: Results of the present study suggest that the antiarthritic activity of MS was due to the interplay between its anti-inflammatory and disease modifying activities, thus supporting its use in traditional medicine for the treatment of RA.

Evaluation of the disease modifying activity of Colchicum luteum Baker in experimental arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Colchicum luteum (CL) has been traditionally used in the Unani system of medicine as a chief ingredient of many polyherbal formulations for the treatment of joint pain and rheumatoid arthritis (RA). AIM OF THE STUDY: To evaluate the antiarthritic activity of CL hydroalcoholic extract (CLHE) in formaldehyde and complete Freund's adjuvant (CFA) induced arthritis. MATERIALS AND METHODS: Arthritis was induced by administration of either formaldehyde (2% v/v) or CFA into the subplantar surface of the hind paw of the animal. Joint swelling was measured on days 8, 9 and 10 in formaldehyde induced arthritis and days 3, 7, 14 and 21 in CFA induced arthritis. In order to evaluate the effect of CLHE on disease progression, serum TNF-α level and synovial expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1ß) was determined in CFA induced arthritis. RESULTS: CLHE produced a significant and dose dependent inhibition of joint swelling during the entire duration of the study in both, formaldehyde and CFA induced arthritis. Serum TNF-α level was also reduced significantly in a dose dependent manner in all the CLHE treated groups. The expression of proinflammatory mediators (TNF-R1, IL-6 and IL-1ß) was also found to be less in the CLHE treated group as compared to control. CONCLUSION: We believe that the antiarthritic activity of CLHE was due to its modulatory effect on the expression of proinflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of CL in the treatment of RA and other inflammatory joint disorders.

Therapeutic potential of herbal drugs in cerebral ischemia.

Stroke is one of the most important causes of mortality and morbidity in the world. Prevention and effective treatment of stroke is of the utmost importance. Cerebral ischemia causes disturbances in a variety of cellular and molecular mechanisms, including oxidative phosphorylation, membrane function, neurotransmitter release, and free radical generation. It has been years since tissue-type plasminogen activator (t-PA) became the first medication approved by the FDA for the management of stroke, with limited success. Thrombolytic therapy is the most effective therapeutic strategy for the prevention of brain injury and reduction of mortality in patients with cerebral infarction. However, a combination of established thrombolytic therapy and effective neuronal protection therapy may have more beneficial effects for patients with cerebral infarction. Because clinical trials of pharmacological neuroprotective strategies in stroke have been disappointing, attention has turned towards approaches which include herbal drugs that can be used in limiting the neurological damage associated with stroke. Herbal drugs may be used as prophylactic treatment in patients with high risk of stroke. Herbals drugs have been described in ancient systems of medicine for the treatment of various ailments associated with stroke and have more recently been reported to be beneficial in treating stroke. However, the strength of evidence to support the use of these herbal drugs is unclear. This review focuses on putative mechanisms underlying the beneficial effects of herbal drugs in patients with stroke and on the possibility of herbal drugs to increase the therapeutic time window in patients with cerebral ischemia.

Evaluation of antitussive activity of formulations with herbal extracts in sulphur dioxide (SO2) induced cough model in mice.

Cough is the most common symptom of respiratory diseases. When cough becomes serious, opioids are effective, but they have side effects like sedation, constipation, some addiction liability and also compromise the respiratory function. Therefore, there is need to have effective anti-tussive agent which do not have respiratory suppressant activity. The present study was carried out to evaluate anti-tussive activity of combination of herbal drugs as formulations in sulphur dioxide (SO2)-induced cough model in mice. Albino mice of either sex, weighing 25-30 g were divided into eight groups, (n = 6). Group 1 served as normal control, group 2 mice were given distilled water, group 3 was positive control and received codeine sulphate (10 mg/kg, p.o.) and group 4, 5, 6, 7 received coded 1 formulations 1, 2, 3 and 4 respectively at a dose of 0.3 ml/mice, orally, while group VIII was the vehicle control. Thirty minutes later, the mice were exposed to sulphur dioxide again for 45 sec. The mice were then placed in an observation chamber for counting of cough bouts, by two independent observers, for five minutes. All the formulations used showed significant antitussive activity in sulphur dioxide induced cough model. Thus, these formulations can prove to be useful for alleviating cough.