Volatile Oil Containing Plants as Phytopharmaceuticals to Treat Psoriasis: A Review.

INTRODUCTION: Psoriasis is a chronic skin condition caused by an autoimmune response that accelerates the life cycle of skin cells, resulting in the characteristic symptoms of scaling, inflammation, and itching. METHODS: Palliative treatment options for psoriasis often prioritize the use of volatile oils. These oils contain monoterpenes, sesquiterpenes, and phenylpropanoids that are intricately linked to the molecular cascades involved in the pathogenesis and symptoms of psoriasis. To evaluate the antipsoriatic efficacy of volatile oils and their components, we conducted a systematic review of scientific studies. Our literature search encompassed various online databases, including PubMed, BIREME, SCIELO, Open Grey, Scopus, and ScienceDirect. The selected studies included experimental in vitro/in vivo assessments as well as clinical studies that examined the potential of volatile oils and their extracts as antipsoriatic agents. We excluded conference proceedings, case reports, editorials, and abstracts. Ultimately, we identified and evaluated a total of 12 studies for inclusion in our analysis. RESULTS: The data collected, compiled, and analyzed strongly support the interaction between volatile oils and their constituents with the key molecular pathways involved in the pathogenesis of psoriasis and the development of its symptoms. Volatile oils play a significant role in the palliative treatment of psoriasis, while their chemical constituents have the potential to reduce the symptoms and recurrence of this condition. CONCLUSION: The current review highlights that the constituents found in volatile oils offer distinct chemical frameworks that can be regarded as promising starting points for the exploration and development of innovative antipsoriatic agents.

Development and biological evaluation of protective effect of kidney targeted N-acetylated chitosan nanoparticles containing thymoquinone for the treatment of DNA damage in cyclophosphamide-induced haemorrhagic cystitis.

Thymoquinone (TQ), the most prominent constituent of Nigella sativa seeds, essential oil, is reported to possess an organ protective effect via Nrf2 expression and activation of Phase-II antioxidant enzymes. Haemorrhagic cystitis is the sudden onset of haematuria combined with bladder pain and irritable bladder symptoms are the known toxic effects of cyclophosphamide (CYP) chemotherapy. The objective of the present study was to investigate and compare the protective effect of thymoquinone (TQ) and thymoquinone nanoparticles (TQ-NP) in the kidney against CYP-induced haemorrhagic cystitis. Primarily, TQ-NP was fabricated by synthesis of N-acetylated chitosan and nanoparticle preparation by the ionic gelation technique. They were characterized by particle size, polydispersive index (PDI), zeta potential, entrapment efficiency (EE), SEM, and dynamic scattering calorimetry (DSC). Moreover, fluorescein isothiocyanate (FITC) labeled NPs were prepared for biodistribution studies. The protective mechanisms of TQ-NP included its anti-inflammatory activity, inhibitory effects on cytokine levels, and protection against the DNA damage in the bladder epithelium. The cystitis was induced in rats by orally administering 200 mg/kg of CYP. The dose-dependent protective effect of the TQ-NP was determined by intravenously administering 1, 2, and 5 mg/kg of the TQ-NP to CYP-treated rats. The present study revealed that the TQ-NP prepared by ionic gelation method provides kidney targeted delivery of TQ as compared to TQ solution. The mean particle size, PDI, and %EE of TQ-NP were 272.6 nm, 0.216, 70.81 ± 0.12% respectively. The zeta potential of thymoquinone-loaded nanoparticles was found to be -20.7 mV and - 22.6 mV respectively before and after lyophilization. SEM study also confirmed the small size and spherical shape. Pharmacokinetic studies revealed the improvement in half-life and prolonged action of the TQ-NP as compared to the TQ solution. Also, TQ-NP administration showed more protection against the characteristic histological alterations in the bladder in comparison to TQ solution. The present study indicates that TQ-NP exerts potent anti-oxidant, DNA protective and cytokine inhibitory activity at considerably lower concentrations as compared to plain TQ solution. The nano formulation of TQ using N-acetylated chitosan provides effective kidney targeted delivery of TQ, which in turn improves its retention and protective efficacy against CYP-induced haemorrhagic cystitis.

Aloin alleviates doxorubicin-induced cardiotoxicity in rats by abrogating oxidative stress and pro-inflammatory cytokines.

PURPOSE: Aloin, an anthraquinone present in the aloe species, possesses antiangiogenic, chemopreventive and antioxidant properties. It exerts cytotoxicity against breast cancer and ovarian cancer cell lines. These properties of aloin project it as a chemopreventive adjuvant to anticancer chemotherapy. METHODS: We evaluated the effect of concurrent oral administration of aloin against doxorubicin (DOX)-induced cardiotoxicity in rats. The protective effects of aloin against DOX-induced toxicity were evident as a statistically significant inhibition of a rise in the biochemical markers of myocardial damage including lactate dehydrogenase (LDH), creatinine kinase-myocardial band (CK-MB), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). RESULTS: Aloin dose dependently inhibited the DOX-induced changes in ECG like increased ST-height and prolonged QT interval. It protected heart against the lipid peroxidation and restored the levels of antioxidative defenses: reduced glutathione, catalase and superoxide dismutase. Aloin prominently reduced the levels of proinflammatory cytokines- TNF-α, IL-1ß and IL-6. Notably, the significant protective effects of aloin were evident even at the strikingly lower doses of 1 and 5 mg/kg per day. CONCLUSION: Our results highlight the necessity to further investigate the chemopreventive effects of aloin against other chemotherapeutic agents.

Disulfiram and Its Copper Chelate Attenuate Cisplatin-Induced Acute Nephrotoxicity in Rats Via Reduction of Oxidative Stress and Inflammation.

The use of cisplatin (CP) in chemotherapy of resistant cancers is limited due to its dose-dependent nephrotoxicity. Disulfiram (DSF), the aversion therapy for alcoholism, has recently emerged as an anticancer and chemopreventive agent. Its anticancer activity is potentiated in the presence of copper. However, such use of copper leads to several adverse effects. In the present study, the protective effect of DSF and its copper chelate (Cu-DEDC) against CP-induced nephrotoxicity in rats was evaluated. Nephrotoxicity was induced by a single intraperitoneal injection of CP (5 mg/kg). The treatment groups included control (vehicle treated), CP (CP-treated), CP + DSF (CP followed by DSF), CP + DSF + Cu (CP followed by DSF and CuCl2), CP + Cu-DEDC (CP followed by Cu-DEDC), and CP + AMF (amifostine pre-treated and CP-treated). The DSF, Cu-DEDC, and CuCl2 were administered orally at 50 mM/kg/day dose for 5 days post CP injection. AMF served as a standard chemo protectant, administered intravenously 30 min prior to CP. The markers of oxidative stress, inflammation, and kidney function estimated on the 6th day revealed that both DSF and Cu-DEDC significantly attenuated the CP-induced rise in the serum/urine creatinine and blood urea nitrogen (BUN). The CP-induced rise in serum alkaline phosphatase (ALPase) was reversed by these drugs. Both drugs reduced the levels of malondialdehyde and nitric oxide (NO) in kidney tissues. These drugs reversed CP-induced depletion of SOD, catalase, and GSH in the kidneys. There was a significant reduction in the CP-induced TNF-α and IL-1ß production along with prevention of histological alterations. Above observations indicate that DSF and Cu-DEDC may have significance as adjuvants to protect against CP-induced nephrotoxicity.

Animal Models of Inflammation for Screening of Anti-inflammatory Drugs: Implications for the Discovery and Development of Phytopharmaceuticals.

Inflammation is one of the common events in the majority of acute as well as chronic debilitating diseases and represent a chief cause of morbidity in today's era of modern lifestyle. If unchecked, inflammation leads to development of rheumatoid arthritis, diabetes, cancer, Alzheimer's disease, and atherosclerosis along with pulmonary, autoimmune and cardiovascular diseases. Inflammation involves a complex network of many mediators, a variety of cells, and execution of multiple pathways. Current therapy for inflammatory diseases is limited to the steroidal and non-steroidal anti-inflammatory agents. The chronic use of these drugs is reported to cause severe adverse effects like gastrointestinal, cardiovascular, and renal abnormalities. There is a massive need to explore new anti-inflammatory agents with selective action and lesser toxicity. Plants and isolated phytoconstituents are promising and interesting sources of new anti-inflammatories. However, drug development from natural sources has been linked with hurdles like the complex nature of extracts, difficulties in isolation of pure phytoconstituents, and the yield of isolated compounds in minute quantities that is insufficient for subsequent lead development. Although various in-vivo and in-vitro models for anti-inflammatory drug development are available, judicious selection of appropriate animal models is a vital step in the early phase of drug development. Systematic evaluation of phytoconstituents can facilitate the identification and development of potential anti-inflammatory leads from natural sources. The present review describes various techniques of anti-inflammatory drug screening with its advantages and limitations, elaboration on biological targets of phytoconstituents in inflammation and biomarkers for the prediction of adverse effects of anti-inflammatory drugs. The systematic approach proposed through present article for anti-inflammatory drug screening can rationalize the identification of novel phytoconstituents at the initial stage of drug screening programs.

Ultra-diluted Toxicodendron pubescens attenuates pro-inflammatory cytokines and ROS- mediated neuropathic pain in rats.

Despite the availability of multiple therapeutic agents, the search for novel pain management of neuropathic pain is still a challenge. Oxidative stress and inflammatory signaling are prominently involved in clinical manifestation of neuropathic pain. Toxicodendron pubescens, popularly known as Rhus Tox (RT) is recommended in alternative medicines as an anti-inflammatory and analgesic remedy. Earlier, we reported anti-inflammatory, anti-arthritic and immunomodulatory activities of Rhus Tox. In continuation, we evaluated antinociceptive efficacy of Rhus Tox in the neuropathic pain and delineated its underlying mechanism. Initially, in-vitro assay using LPS-mediated ROS-induced U-87 glioblastoma cells was performed to study the effect of Rhus Tox on reactive oxygen species (ROS), anti-oxidant status and cytokine profile. Rhus Tox decreased oxidative stress and cytokine release with restoration of anti-oxidant systems. Chronic treatment with Rhus Tox ultra dilutions for 14 days ameliorated neuropathic pain revealed as inhibition of cold, warm and mechanical allodynia along with improved motor nerve conduction velocity (MNCV) in constricted nerve. Rhus Tox decreased the oxidative and nitrosative stress by reducing malondialdehyde (MDA) and nitric oxide (NO) content, respectively along with up regulated glutathione (GSH), superoxide dismutase (SOD) and catalase activity in sciatic nerve of rats. Notably, Rhus Tox treatment caused significant reductions in the levels of tumor necrosis factor (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) as compared with CCI-control group. Protective effect of Rhus Tox against CCI-induced sciatic nerve injury in histopathology study was exhibited through maintenance of normal nerve architecture and inhibition of inflammatory changes. Overall, neuroprotective effect of Rhus Tox in CCI-induced neuropathic pain suggests the involvement of anti-oxidative and anti-inflammatory mechanisms.

D-pinitol attenuates cisplatin-induced nephrotoxicity in rats: Impact on pro-inflammatory cytokines.

Cisplatin has been widely used as a first-line agent against various forms of solid cancers. However, nephrotoxicity is the major limiting factor for its clinical use. Several clinical and pre-clinical studies have suggested different strategies for the reduction of cisplatin-induced nephrotoxicity. The present study was conducted to investigate the efficacy of D-Pinitol, against cisplatin-induced nephrotoxicity in Swiss albino mice. A single intraperitoneal injection of cisplatin (20 mg/kg) was used to induce nephrotoxicity in mice. Administration of cisplatin in mice is linked with elevated oxidative stress, imbalanced biochemical parameters, apoptosis and stimulation of mitogen-activated protein kinase (MAPK) pathway. D-Pinitol is a member of the flavonoid family and a chief constituent of Sutherlandia fruitesecnce. It was administered with saline water (10, 20, 40 mg/kg, p.o.) for seven consecutive days after a single dose of cisplatin. At the end of experiment, animals were sacrificed and biochemical parameters in serum and urine were recorded. Kidneys were isolated for the estimation of tumor necrosis factor-alpha, interleukin-1ß, interlukin-6 levels and histopathological evaluations. It was noted that D-Pinitol significantly ameliorated biochemical levels of serum and urinary creatinine and blood urea nitrogen. Tissue homogenate levels of TNF-α, IL-6, IL-1ß and the renal expression of tissue nitrites were also significantly decreased in D-Pinitol treated mice. These results were supplemented by histopathological findings. This study highlights the potential role of D-Pinitol against cisplatin-induced toxicity, exhibited through favorable alterations in biochemical and histological changes as well as reduction in oxidative stress and cytokine levels.

Anti-inflammatory activity of bartogenic acid containing fraction of fruits of Barringtonia racemosa Roxb. in acute and chronic animal models of inflammation.

The fruits of Barringtonia racemosa are traditionally used in Indian medicine for the treatment of pain and inflammatory conditions. In this study, a fraction of ethyl acetate extract of fruits of B. racemosa (BREAF) was investigated for anti-inflammatory activity in experimental models of acute and chronic inflammation. Activity against acute inflammation was evaluated in inflammogens induced rat paw edema models. Whereas, effect in chronic inflammation was evaluated in cotton pellet granuloma and oxazolone induced delayed type hypersensitivity (DTH) model in mice. The BREAF exhibited dose dependent anti-inflammatory activity in both acute and chronic models at oral doses of 5, 10 and 20 mg/kg. BREAF inhibited both phases of carrageenan induced rat paw inflammation. The reduction in paw inflammation by BREAF was also evident in histamine and serotonin induced inflammation in rats. Effect of BREAF on DTH indicates inhibition of immune mediated inflammation. The reduction in cotton pellet granuloma by BREAF treatment shows inhibition of proliferative changes associated with chronic inflammation. Analysis of BREAF after chromatographic separations showed presence of bartogenic acid as a major constituent. Hence, it is proposed that anti-inflammatory effects of BREAF can be partially attributed to its bartogenic acid content. The minute doses at which this fraction shows anti-inflammatory effects emphasizes the need for further investigations on its efficacy in the immuno-inflammatory conditions.

Chemomodulatory Potential of Bartogenic Acid Against DMBA/Croton Oil Induced Two-Step Skin Carcinogenesis in Mice.

Barringtonia racemosa fruits are believed to be useful in cancer treatment in Ayurveda, the Indian system of medicine. In present study, bartogenic acid (BA), a triterpenoid constituent of Barringtonia fruits was evaluated for its cytotoxicity property using the human skin carcinoma cell line (SCC-13) and human peripheral blood mononuclear cells (PBMC). The chemopreventive efficacy of BA was evaluated against the DMBA/Croton oil-induced skin carcinogenesis in mice.BA was orally administered at the doses of 1, 2 or 4 mg/kg/day or applied topically every day for 12 weeks following DMBA application. The in vitro data from cell lines revealed that BA induces cytotoxicity against the SCC-13 cells (IC50=7.5 µM). It was found 4.05 times more selective to exert cytotoxicity against SCC-13 as compared to the PBMC (IC50=30.4 µM). The in vivo datacollected from mice model of DMBA/Croton oil-induced skin carcinogenesis revealed that BA administered orally or applied topically, both reduced the precancerous skin lesions andthe incidence of tumor bearing. The oral doses of BA (2 and 4 mg/kg) and topical treatment significantly reduced the incidence and number of skin papillomas. At these doses, BA also increased the activities of catalase and superoxide dismutase and induced an increase in glutathionecontent and inhibited lipid peroxidation in the skin. These findings reveal the chemopreventive efficacy of BA and also demonstrate that it contributes to the cytotoxic and antioxidative effects of Barringtonia racemosa fruits. The study also validates the traditional claims of Barringtonia fruits and provides a scientific basis of its chemopreventive property.

Pentacyclic Triterpenoids Inhibit IKKß Mediated Activation of NF-κB Pathway: In Silico and In Vitro Evidences.

Pentacyclic Triterpenoids (PTs) and their analogues as well as derivatives are emerging as important drug leads for various diseases. They act through a variety of mechanisms and a majority of them inhibit the nuclear factor kappa-beta (NF-κB) signaling pathway. In this study, we examined the effects of the naturally occurring PTs on IκB kinase-ß (IKKß), which has great scientific relevance in the NF-κB signaling pathway. On virtual screening, 109 PTs were screened through the PASS (prediction of activity spectra of substances) software for prediction of NF-κB inhibitory activity followed by docking on the NEMO/IKKß association complex (PDB: 3BRV) and testing for compliance with the softened Lipinski's Rule of Five using Schrodinger (LLC, New York, USA). Out of the projected 45 druggable PTs, Corosolic Acid (CA), Asiatic Acid (AA) and Ursolic Acid (UA) were assayed for IKKß kinase activity in the cell free medium. The UA exhibited a potent IKKß inhibitory effect on the hotspot kinase assay with IC50 of 69 µM. Whereas, CA at 50 µM concentration markedly reduced the NF-κB luciferase activity and phospho-IKKß protein expressions. The PTs tested, attenuated the expression of the NF-κB cascade proteins in the LPS-stimulated RAW 264.7 cells, prevented the phosphorylation of the IKKα/ß and blocked the activation of the Interferon-gamma (IFN-γ). The results suggest that the IKKß inhibition is the major mechanism of the PTs-induced NF-κB inhibition. PASS predictions along with in-silico docking against the NEMO/IKKß can be successfully applied in the selection of the prospective NF-κB inhibitory downregulators of IKKß phosphorylation.