Zinc and L-carnitine combination with or without methotrexate prevents intestinal toxicity during arthritis treatment via Nrf2/Sirt1/Foxo3 pathways: an In vivo and molecular docking approach.

Methotrexate (MTX) is an antifolate that is inescapable and widely used to treat autoimmune diseases and is the gold standard medicine for the arthritic condition. Despite its importance, it is more prone to gastrointestinal toxicity, which is most common in arthritis patients during MTX treatment. Combination therapies are required to ensure MTX's antiarthritic activity while providing gastrointestinal protection. Zinc (Zn) and L-carnitine (Lc) are well-known potent antioxidants and anti-inflammatory supplements with promising results in pre-clinical studies. Arthritis was induced in Wistar rat's ankles with Freund's adjuvant and treated with either MTX (2.5 mg/kg b.w per week for two weeks) or Zn (18 mg/kg b.w. per day) Lc (200 mg/kg b.w. per day) individually or in combination (MTX + Zn Lc). The antiarthritic effects were evaluated by body weight, paw volume, ankle tissue, and joint histopathology. At the same time, anti-toxicity/gastrointestinal protective activity was examined by tissue oxidative stress markers, antioxidants, mitochondrial function, inflammatory mediators, and antioxidant signaling proteins and their binding mechanism. Repercussions of MTX intoxication induced upregulation of oxidative stress markers, antioxidant depletion, ATP depletion, decreased expression of Nrf2/Sirt1/Foxo3, and the overexpression of inflammatory mediators attenuated by co-treatment with Zn Lc. Zn Lc markedly mitigated MTX-instigated intestinal injury by activating antioxidant signaling mechanisms Nrf2/Sirt1/Foxo3 signaling and tissue architectural anomalies and exhibited an enhanced antiarthritic effect. In conclusion, we report that Zn Lc and MTX combination could presumably protect the intestine from low-dose MTX which managed arthritis but induced severe intestinal damage with increased inflammation and downregulated Nrf2/Sirt1/Foxo3 pathway.

HPV-associated cancers: insights into the mechanistic scenario and latest updates.

Cancer and related diseases are the second leading cause of death worldwide. The human papillomavirus (HPV) is an infectious agent that can be spread mainly through sexual contact and has been linked to several malignancies in both sexes. HPV is linked to almost all cases of cervical cancer. It is also linked to many head and neck cancer (HNC) cases, especially oropharyngeal cancer. Also, some HPV-related cancers, like vaginal, vulvar, penile, and anal cancers, are related to the anogenital area. Over the past few decades, testing for and preventing cervical cancer has improved, but anogenital cancers are still harder to confirm. HPV16 and HPV18 have been extensively researched due to their significant carcinogenic potential. The products of two early viral genes, E6 and E7, have been identified as playing crucial roles in cellular transformation, as emphasized by biological investigations. The complete characterization of numerous mechanisms employed by E6 and E7 in undermining the regulation of essential cellular processes has significantly contributed to our comprehension of HPV-induced cancer progression. This review focuses on the various types of cancers caused by HPV infection and also sheds light on the signaling cascades involved in the same.

L-carnitine and Zinc supplementation impedes intestinal damage in methotrexate-treated adjuvant-induced arthritis rats: Reinstating enterocyte proliferation and trace elements.

BACKGROUND: Methotrexate (MTX), a folic acid analogue, is used as a first-line treatment for rheumatoid arthritis (RA) since it has more therapeutic mechanisms than any other drug. Being an undeniable drug for the treatment of arthritis, even low-dose MTX provokes intestinal toxicity as a primary adverse effect and does not revive an anti-inflammatory element. Thus, our study aims to elucidate the anti-arthritic and prophylactic activity of supplements L-carnitine (L) and zinc (Z) against MTX-mediated intestinal damage in arthritis rats. METHODS: The rats were assessed for arthritic parameters such as body weight, paw volume, x-ray scan, and serum trace elements level. To analyze the toxic effects of MTX in the rats, intestine pH, mucosal weight, digestive enzymes, myeloperoxidase, histopathological, and immunohistochemical analysis were performed. RESULTS: Our study demonstrated that the arthritic parameters have shown that MTX has an ameliorative effect on arthritic rats. Besides, our findings showed that low-dose MTX (2.5 mg/kg b.w.) given once a week for two weeks during arthritis treatment had toxic effects in the rat's intestine, as evidenced by changes in intestine pH and mucosal weight, decreased digestive enzymes, increased MPO, and degenerative changes in histopathological analysis. Concurrent therapy of LZ with MTX, on the other hand, restored the modifications in these parameters. CONCLUSION: MTX in combination with LZ effectively manages arthritis than monotherapy and significantly prevents MTX-induced intestinal damage in arthritis rats. Thus, LZ could be used as an improved therapeutic and safety for MTX-instigated intestinal damage during arthritis treatments. Therefore, our combination of L-carnitine and zinc with MTX would be promising prophylactic activity for arthritis patients.

Caesalpinia bonducella mitigates oxidative damage by paracetamol intoxication in the kidney and intestine via modulating pro/anti-inflammatory and apoptotic signaling: an In vivo mechanistic insight.

Protracted use of paracetamol at therapeutic/toxic doses readily induces major organ toxicity and poor clinical efficacy. Caesalpinia bonducella seeds possess a diverse range of biological and therapeutic activities. Thus, our study aimed to scrutinize the toxic effects of paracetamol and the potential renal and intestinal protective effects of Caesalpinia bonducella seed extract (CBSE). To Wistar rats, CBSE was administered for 8 days (300 mg/kg, p.o.) with or without paracetamol (2000 mg/kg, p.o.) on the 8th day. Pertinent toxicity assessments in the kidney and intestine were analyzed at the end of the study. The CBASE's phytochemical components were examined using gas chromatography-mass spectrometry (GC-MS). After the study period, study findings evidenced that paracetamol intoxication induced elevation of renal enzyme indicators, oxidative damage, imbalance with the pro/anti-inflammatory production and pro/anti-apoptotic mediators, and tissue injury; all repercussions were alleviated by pre-treatment with CBASE. CBASE considerably reduced (P < 0.05) paracetamol-induced kidney and intestine injury by limiting caspase-8/3 signaling and amplification of inflammation in renal and intestinal tissue by significantly reducing pro-inflammatory cytokine production. As per the GC-MS report, three main bioactive components-Piperine, Isocaryophyllene, and Tetradec-13-en-11-yn-1-ol were predominant and have protective activities. Our study ascertains that CBSE pre-treatment exerts potent renal and intestine protection against paracetamol intoxication. Thus, CBSE could be a prospective therapeutic candidate for protecting the kidney and intestine from the severity of paracetamol intoxication.

The NEK family of serine/threonine kinases as a biomarker for cancer.

Cancer is defined by unrestrained cell proliferation due to impaired protein activity. Cell cycle-related proteins are likely to play a role in human cancers, including proliferation, invasion, and therapeutic resistance. The serine/threonine NEK kinases are the part of Never In Mitosis A Kinases (NIMA) family, which are less explored kinase family involved in the cell cycle, checkpoint regulation, and cilia biology. They comprise of eleven members, namely NEK1, NEK2, NEK3, NEK4, NEK5, NEK6, NEK7, NEK8, NEK9, NEK10, and NEK11, located in different cellular regions. Recent research has shown the role of NEK family in various cancers by perversely expressing. Therefore, this review aimed to provide a systematic account of our understanding of NEK kinases; structural details; and its role in the cell cycle regulation. Furthermore, we have comprehensively reviewed the NEK kinases in terms of their expression and regulation in different cancers. Lastly, we have emphasized on some of the potential NEK inhibitors reported so far.

Molecular toxicity of methotrexate in rheumatoid arthritis treatment: A novel perspective and therapeutic implications.

Rheumatoid arthritis (RA) is an autoimmune inflammatory systematic complication which is a chronic disorder that severely affects bones and joints and results in the quality of life impairment. Methotrexate (MTX), an FDA-approved drug has maintained the standard of care for treating patients affected with RA. The mechanism of MTX includes the inhibition of purine and pyrimidine synthesis, suppression of polyamine accumulation, promotion of adenosine release, adhesion of the inflammatory molecules, and controlling of cytokine cascade in RA. The recommended dose for RA patients is 5-25 mg of MTX per week, depending on the severity of the disease but MTX has proven to be cytotoxic with side effects affecting various tissues when treating RA patients even with low doses over a prolonged period of time. The mechanism of such toxicity is not entirely understood. This review strives to understand it by correlating the different pathways, including MTX in folate metabolism, Sirt1/Nrf2/γ-gcs, and γ-gcs/CaSR-TNF-α/NF-kB signaling. In addition to this, the importance of targeted therapy combination with MTX on RA treatment and combinations approved from the clinical trials are also briefly discussed. Overall, this review elucidates the various MTX molecular mechanisms and toxicity at the molecular level, the limitations, and the scope for future directions.

The potential effect of phytochemicals and herbal plant remedies for treating drug-induced hepatotoxicity: a review.

Drug-induced liver injury significantly caused by synthetic drugs, and other xenobiotics contribute to clinical hepatic dysfunction, which has been a substantial challenge for both patients and physicians. Traditional medicines used as an alternative therapy because of their pharmacological benefits, less or no side effects, and enormous availability in nature. Phytochemicals are essential ingredients of plants that reduce necrotic cell death, restore the antioxidant defence mechanism, limit oxidative stress, and prevent the inflammation of tissue and dysfunction of the mitochondria. In this review, we principally focused on the potential effect of the herbal plants and their phytochemicals in treating drug-induced hepatotoxicity.

A role of connexin 43 on the drug-induced liver, kidney, and gastrointestinal tract toxicity with associated signaling pathways.

Drug-induced organ toxicity/injury, especially in the liver, kidney, and gastrointestinal tract, is a systematic disorder that causes oxidative stress formation and inflammation resulting in cell death and organ failure. Current therapies target reactive oxygen species (ROS) scavenging and inhibit inflammatory factors in organ injury to restore the functions and temporary relief. Organ cell function and tissue homeostasis are maintained through gap junction intercellular communication, regulating connexin hemichannels. Mis-regulation of such connexin, especially connexin (Cx) 43, affects a comprehensive process, including cell differentiation, inflammation, and cell death. Aim to describe knowledge about the importance of connexin role and insights therapeutic targeting. Cx43 misregulation has been implicated in recent decades in various diseases. Moreover, in recent years there is increasing evidence that Cx43 is involved in the toxicity process, including hepatic, renal, and gastrointestinal disorders. Cx43 has the potential to initiate the immune system to cause cell death, which has been activated in the acceleration of apoptosis, necroptosis, and autophagy signaling pathway. So far, therapies targeting Cx43 have been under inspection and are subjected to clinical trial phases. This review elucidates the role of Cx43 in drug-induced vital organ injury, and recent reports compromise its function in the major signaling pathways.

Effect of Baricitinib on TPA-induced psoriasis like skin inflammation.

Psoriasis is a chronic inflammatory disorder of the skin and is characterized by hyper-dividing keratinocytes. This hyper-proliferation of keratinocytes is due to the high level of inflammatory cytokines. In this study, we evaluated the effect of topically applied Baricitinib, JAK1/2 inhibitor on chronic 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced psoriasis model in mice. To our knowledge, this is the first report evaluating the topical route of administration of Baricitinib in the context of psoriasis in vivo. TPA-induced inflammation was induced by the topical application of TPA in both ears. Thirty minutes before the application of TPA, the inner and outer surface of each ear was treated with Baricitinib for 6 days. Topical application of Baricitinib inhibited the expression of inflammation markers up-regulated by TPA. Besides, Baricitinib substantially reduced ear swelling, infiltration of leukocytes, the proliferation of epidermal cells, and angiogenesis of the dermal layer. The results suggest that Baricitinib significantly reduced phosphorylation of STAT3 and STAT1 levels in turn attenuating the downstream expression of inflammatory cytokines. Collectively, these results suggest that Baricitinib can be a potential therapeutic through topical route for psoriasis progresses.

Ameliorative activity of aqueous leaf extract from Madhuca longifolia against diclofenac-administered toxicity on rat stomach and intestine.

Madhuca longifolia, a tropical tree used as medicine and food, is known to have a beneficial effect against stomach gastric toxicity. Madhuca longifolia is used in treating cough, skin disease and nerve disorders. Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), with overdosage and prolonged use, is known to cause gastric toxicity. Silymarin (SLY), a polyphenolic antioxidant flavonoid, is a derivative of Silybum marianum extracted from milk thistle seeds and fruits, has been widely used in the treatment of gastric ulcer. SLY was used as the standard drug to compare the effects with the Madhuca longifolia aqueous leaf extract treatment. The aim of the current study is to understand the effect of Madhuca longifolia aq. leaf extract on rat stomach and intestine against diclofenac-administered toxicity. Rats (n = 30) were divided into Group I normal control, Group II treated with diclofenac, Group III treated with diclofenac and Madhuca longifolia leaf extract, Group IV treated with diclofenac and silymarin, and Group V was treated with Madhuca longifolia leaf extract alone. After the study duration, rats were euthanized and tissue samples were analyzed for antioxidant, cytokine, protein expression levels and histopathological changes. Diclofenac treated rats had significant (p < 0.05) changes in levels of antioxidants, cytokines, protein expression and pathological changes as compared to rats treated with Madhuca longifolia. This study demonstrated that Madhuca longifolia leaf extract had gastroprotective activity in rats treated with diclofenac.

Aqueous leaves extract of Madhuca longifolia attenuate diclofenac-induced hepatotoxicity: Impact on oxidative stress, inflammation, and cytokines.

Diclofenac is a Non-Steroidal Anti-inflammatory drug which is used as an analgesic. It is known to cause heptotoxicity on over dose and long term usage. Madhuca longifolia is an evergreen tree found widely in India that is known to have several ethnomedical uses. The aim of our study is to evaluate the beneficial effect of the aqueous leaf extract of M. longifolia against diclofenac-induced toxicity. Rats were dived into five groups of six rats each. Group-I was normal control. Group-II was administered with diclofenac (50 mg/kg. b.w./day, i.p) on 4th and 5th day. Group-III rats were treated with aqueous leaf extract of M. longifolia (500 mg/kg b.w./day, oral) for 5 consecutive days and diclofenac (50 mg/kg. b.w./day, i.p) was given on 4th and 5th day. Silymarin (25 mg/kg. b.w./day, oral) was used as standard drug which was given to the rats of group-IV along with diclofenac on 4th and 5th day. Aqueous leaf extract of M. longifolia (500 mg/kg b.w./day, oral) alone was administered in group-V. After the study period, the rats were evaluated for liver enzyme markers, antioxidant parameters, histopathological changes, and cytokines levels. The hepatic proinflammatory mediator cytokines like TNF-α, IL-6, and IL-1ß were evaluated through ELISA. The protein expression of Caspase-3, COX-2, and NF-κB were analysed through Western blotting techniques. Aqueous leaves extract of M. longifolia was able to normalize the changes caused by diclofenac. Current study indicatesthe protective effect of the aqueous leaves extract of M. longifolia against diclofenac-induced toxicity.

Evidence of antidiabetic activity of Spirulina fusiformis against streptozotocin-induced diabetic Wistar albino rats.

The aim of our study is to investigate the protective effect of Spirulina fusiformis against streptozotocin-induced diabetes in Wistar albino rats. Rats were divided into five groups: group I was normal control, group II was diabetic control (50 mg/kg b.w. of streptozotocin, i.p.), group III was Spirulina fusiformis (400 mg/kg b.w., p.o.) treated diabetic rats; group IV was Glibenclamide (0. 6 mg/kg b.w., p.o.) treated diabetic rats and group V was treated with Spirulina fusiformis (400 mg/kg b.w., p.o.) alone. There was significant elevation in the levels of blood glucose, serum lipid profile and serum renal markers (total protein, urea, creatinine and uric acid) in the diabetic rats. Also, diabetic rats showed significantly (P < 0.05) reduced antioxidant status (reduced levels of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione; increased levels of TBARS), impaired oral glucose tolerance and elevated HbA1C. Spirulina fusiformis was able to normalize the above mentioned parameters. Significant histopathological changes were found in the pancreas, liver and kidney sections of the diabetic control group while treatment with Spirulina fusiformis was able to minimize the extent of tissue damage. Current study shows that Spirulina fusiformis possesses significant antidiabetic and antihyperlipidemic effects in streptozotocin-induced diabetic rats by effectively reducing the rise in blood glucose levels and lipid profile.

Diclofenac-induced renal toxicity in female Wistar albino rats is protected by the pre-treatment of aqueous leaves extract of Madhuca longifolia through suppression of inflammation, oxidative stress and cytokine formation.

CONTEXT: Kidney has a vital role in renal clearance, maintenance of blood pressure, elimination of toxic products and formation of prostaglandins. Certain medications are known to cause renal injury on its frequent usage and high dosage. Diclofenac is a non-steroidal anti-inflammatory drug which is used in the treatment of pain and arthritis. Madhuca longifolia is a deciduous tree which is known to the have anti-microbial, anti-ulcer, hepatoprotective, anti-diabetic, anti-inflammatory and analgesic activity. The aim of the present study is to evaluate the beneficial effect of aqueous leaf extract of Madhuca longifolia against DFC-induced renal toxicity in female Wistar albino rats. METHODS: Thirty female Wistar albino rats were divided into five groups and the drugs were administrated specifically on each group. After the treatment period, the rats were sacrificed to evaluate the significant changes in renal enzyme markers, antioxidant activities in kidney tissue homogenate and plasma, renal histopathology and protein expression levels. The cytokines like TNF-α, IL-6 and IL-1ß were measured through ELISA techniques and the levels of Caspase-3, COX-2 and NF-κB were measured through western blotting techniques. DiscussionMadhuca longifolia was observed to show a better result in normalizing the toxicity caused by diclofenac. CONCLUSION: The significant result of the aqueous leaf extract ofMadhuca longifolia was due to its ability in restoring renal function by restoring antioxidants and preventing cellular damages.

Comparative Modulation of Levels of Oxidative Stress in the Liver of Anti-Tuberculosis Drug Treated Wistar Rats by Vitamin B12, Beta-Carotene, and Spirulina fusiformis: Role of NF-κB, iNOS, IL-6, and IL-10.

Isoniazid (INH) and Rifampicin (RIF) are known hepatotoxic agents. We compared the efficacy of Spirulina fusiformis and its active components vitamin B12 and beta-carotene in attenuating INH and RIF induced hepatotoxicity. We also tried to elucidate the inflammatory mechanism behind anti-tuberculosis drug induced hepatotoxicity. INH and RIF were administered to Wistar albino rats for 28 days to induce hepatotoxicity. S. fusiformis, vitamin B12, and beta-carotene were co-administered with INH and RIF and their hepatoprotective, antioxidant, and immunomodulatory roles were studied through blood and liver analysis. Changes induced by INH and RIF in antioxidants, cytokines (IL-6 and IL-10) and expression of Nuclear Factor-κB (NF-κB) and Nitric Oxide Synthase (iNOS) were also studied. Supplement treatment caused restoration of liver function parameters to normal levels along with reversal of inflammatory changes in IL-6 and IL-10 levels. Liver PCNA, iNOS, and NF-κB expression were reduced in the supplement treated tissues compared to INH and RIF treated rats as evidenced by immunohistochemistry and quantitative PCR. Correlation of IL-6 levels, PCNA, and iNOS with NF-κB showed its pivotal role in the inflammatory process. Study shows the pivotal role of NF-kB and the equivalence in antioxidant efficacy of vitamin B12 and beta-carotene compared to Spirulina fusiformis. J. Cell. Biochem. 118: 3825-3833, 2017. © 2017 Wiley Periodicals, Inc.

Natural remedies for non-steroidal anti-inflammatory drug-induced toxicity.

The liver is an important organ of the body, which has a vital role in metabolic functions. The non-steroidal anti-inflammatory drug (NSAID), diclofenac causes hepato-renal toxicity and gastric ulcers. NSAIDs are noted to be an agent for the toxicity of body organs. This review has elaborated various scientific perspectives of the toxicity caused by diclofenac and its mechanistic action in affecting the vital organ. This review suggests natural products are better remedies than current clinical drugs against the toxicity caused by NSAIDs. Natural products are known for their minimal side effects, low cost and availability. On the other hand, synthetic drugs pose the danger of adverse effects if used frequently or over a long period. Copyright © 2016 John Wiley & Sons, Ltd.

Clinical and experimental research in antituberculosis drug-induced hepatotoxicity: a review / 中西医结合学报

Drug-induced liver injury is the common adverse effect seen in patients receiving antituberculosis drugs (ATDs). There are several risk factors associated with the development of hepatotoxicity in such patients. Though there have been appreciable efforts taken by carrying out studies investigating the efficacy of several natural and synthetic compounds in minimising this effect, the only choice available for clinicians is withdrawal of drugs. This review would give a precise idea of ATD-induced hepatotoxicity, its underlying mechanisms and alternative therapies for the same.

Efficacy of CoenzymeQ10 in inhibiting monosodium urate crystal-induced inflammation in rats.

Gout is a type of arthritis, which could result from the deposition of monosodium urate crystals in joints. It can cause redness, burning pain, inflammation of joints especially in big toe. In this study, we have looked for anti-arthritic effect of coenzyme Q10 (CoQ10) on monosodium urate crystal-induced inflammation in rats and compared it with that of the non-steroidal anti-inflammatory drug, indomethacin. The evaluation was done by measuring the paw volume, antioxidant status, lipid peroxidation, lysosomal enzymes (ß-glcuronidase, ß-galactosidase, N-acetyl-ß-d-glucosaminidase, acid phosphatase) activities and histopathological studies. Paw volume, the levels of lysosomal enzymes, lipid peroxidation were significantly (P<0.05) increased and the antioxidant activity status was in turn decreased in monosodium urate crystal-induced rats. CoQ10 (10mg/kg/b.w. orally) treated monosodium urate crystal-induced rats showed near normal activities of lysosomal enzymes, reduced levels of lipid peroxidation, near normal paw volume and antioxidant status. CoQ10 was also able to minimize mononuclear cell infiltration and damage to articular cartilage. Current study indicates that CoQ10 possesses anti-inflammatory effect against gouty arthritis and can be used to treat acute form of gouty arthritis.

Reparation of Isoniazid and Rifampicin Combinatorial Therapy-Induced Hepatotoxic Effects by Bacopa monnieri.

Drug-induced liver injury is a major challenge in treating tuberculosis with isoniazid (INH) and rifampicin (RIF). This study was aimed at evaluating the protective effects of Bacopamonnieri (Brahmi) against INH and RIF-induced hepatotoxicity in a rat model and also to study the patterns of interaction between pregnane X receptor (PXR) and chosen active compounds of B. monnieri. Hepatotoxicity was induced in the experimental animals by the oral administration of INH and RIF (50 mg/kg b.w. each/day) for 28 days. The effects of co-administration of B. monnieri (500 mg/kg b.w./day) in INH- and RIF-induced rats were studied by the estimation of biochemical analyses. The standard hepatoprotective drug silymarin (25 mg/kg b.w./day) was used for the purpose of comparison. In silico docking experiments were carried out using the PatchDock server and the results were analysed on the PyMol molecular viewer. There was significant reduction in the antioxidant status of INH and RIF-induced rats. Also, there was significant elevation in the levels of serum liver function markers in the INH- and RIF-induced rats. B. monnieri was able to normalise the tested parameters. In silico studies reveal significant interaction between PXR and bacopaside I. B. monnieri exerts significant protective effects against INH and RIF-induced hepatotoxicity in rats.

Efficacy of boswellic acid on lysosomal acid hydrolases, lipid peroxidation and anti-oxidant status in gouty arthritic mice

<p><b>OBJECTIVE</b>To evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice.</p><p><b>METHODS</b>The mice were divided into four experimental groups. Group I served as control; mice in group II were injected with monosodium urate crystal; group III consisted of monosodium urate crystal-induced mice who were treated with boswellic acid (30 mg/kg/b.w.); group IV comprised monosodium urate crystal-induced mice who were treated with indomethacin (3 mg/kg/b.w.). Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-α were determined in control and monosodium urate crystal-induced mice. In addition, the levels of β-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro.</p><p><b>RESULTS</b>The activities of lysosomal enzymes, lipid peroxidation, and tumour necrosis factor-α levels and paw volume were increased significantly in monosodium urate crystal-induced mice, whereas the activities of antioxidant status were in turn decreased. However, these changes were modulated to near normal levels upon boswellic acid administration. In vitro, boswellic acid reduced the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells.</p><p><b>CONCLUSIONS</b>The results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid, which was already well established by several investigators.</p>