Anti-psoriatic effect of Lavandula angustifolia essential oil and its major components linalool and linalyl acetate.

ETHNO-PHARMACOLOGICAL RELEVANCE: Lavender oil (LO) is an aromatic/essential oil extracted from Lavandula angustifolia and traditionally used as an aromatherapy massage oil due to its anti-inflammatory and wound healing property and also for providing the relief in other skin conditions such as psoriasis, dermatitis and eczema. However, LO has not been evaluated scientifically for psoriasis like skin inflammation. AIM OF THE STUDY: This study was aimed to investigate the LO and its major components linalool (L) and linalyl acetate (LA) against psoriasis like skin inflammation. MATERIALS AND METHODS: Anti-psoriatic activity was done using Imiquimod (IMQ) induced psoriasis like skin inflammation in BALB/c mice. Assessment of anti-psoriatic effect of LO, L and LA was done on the basis of change in ear thickness, psoriasis area severity index (PASI) scoring at alternative day, CosCam scoring using skin analyzer equipped with SkinSys software, biochemical, immunohistochemical and histological investigations. Level of effectiveness against psoriasis was investigated by percent reduction in PASI scores, CosCam scores and level of Th-1 and Th-17 cell expressing cytokines, as compared to the diseased mice. RESULTS: Topical application of LO 10% showed 73.67% recovery in PASI and 87% in Th-17 cell-specific cytokines towards normal as compared to disease group. L and LA were identified as the major components of LO and favoured ligands for selected psoriasis targets. At 2% topical dose, L and LA showed 64% and 47.61% recovery in PASI scores, respectively. Both, L and LA showed significant recovery in Th-1 specific TNF-α and IL-1ß however, only L showed significant recovery of Th-17 cytokines (IL-17 and IL-22). In contrast to LA (which restored granulosis), L restored epidermal hyperplasia and parakeratosis toward the normal condition. On the other hand, L also reduced the expression of NF-κß, ccr6 and IL-17, while LA reduced the expression of NF-κß only. At 10% topical dose, LO was observed to be slight irritant while at 2% topical dose, L and LA were found non-irritant to the skin. CONCLUSION: This study proves the effectiveness of LO and its major phytoconstituents linalool and linalyl acetate against IMQ induced psoriasis like skin inflammation and provides the scientific evidence for topical use of lavender oil.

Essential oil from waste leaves of Curcuma longa L. alleviates skin inflammation.

BACKGROUND: Curcuma longa L. is an important industrial crop used by medicinal and cosmetic industries in the world. Its leaves are a waste material after harvesting rhizomes. The aim of the study was to evaluate the chemical and pharmacological profile of essential oil from waste leaves of Curcuma longa (EOCl) against skin inflammation. METHODS: EOCl was subjected to gas chromatography (GC) analysis for identification of essential oil constituents and its anti-inflammatory evaluation through in vitro and in vivo models. RESULTS: Chemical fingerprinting using GC and GC-MS analysis of EOCl revealed the presence of 11 compounds, representing 90.29% of the oil, in which terpinolene (52.88%) and α-phellandrene (21.13%) are the major components. In the in vitro testing EOCl inhibited the production of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) in lipopolysaccharide (LPS) and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in the human keratinocyte cell line (HaCaT). Topical application of EOCl produced anti-inflammatory effects by reducing ear thickness, ear weight and ameliorating the level of pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) at protein and mRNA levels as well as regulating the overproduction of oxidative markers and restoring the histopathological damage in a TPA-induced mouse model of inflammation. CONCLUSION: These findings of topical anti-inflammatory properties of EOCl provide a scientific basis for medicinal use of this plant material against inflammatory disorders.

Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders - A Review.

BACKGROUND: Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases. OBJECTIVE: To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patients regardless of their background on equality basis. RESULTS: Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogenactivated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common antiinflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppresants used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration. CONCLUSION: Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.

In vitro and in vivo immunomodulatory potential of Pedicularis longiflora and Allium carolinianum in alloxan-induced diabetes in rats.

Pedicularis longiflora Rudolph (Orobanchaceae) and Allium carolinianum Linn (Alliaceae) are two important medicinal plants found in trans-Himalayan Changthang. The immunomodulatory potential of these plants has not been explored. In the present study, we evaluated the in vitro and in vivo immunomodulatory potential of P. longiflora and A. carolinianum in alloxan-induced diabetes in Wistar rats. The ethanol extracts of the aerial parts of P. longiflora and whole plant parts of A. carolinianum were used for studying the in vitro immunomodulatory activity using lymphocyte stimulation and cytokine release assays. For the in vivo study, 5 groups of 6 rats per group, including alloxan-induced diabetic and plant extract-treated rats, were evaluated for cell-mediated immune (CMI) and humoral immune (HMI) responses in a 42-day experimental trial using doses of 500mg/kg b.wt. for P. longiflora and 250mg/kgbwt. for A. carolinianum. For P. longiflora, the median effective dose was found to be 500mg/kg. The in vitro lymphocyte stimulation index for P. longiflora was significantly higher (1.73±0.04, p<0.05) than that for A. carolinianum (1.27±0.06). However, the release of transforming growth factor-ß1 (TGF-ß1, 15.63±1.00, p<0.05) by P. longiflora was significantly lower than that by A. carolinianum (21.61±1.19), suggesting a better immune response by P. longiflora than by A. carolinianum. P. longiflora significantly increased the ear thickness (53.12%), inflammatory cellular infiltration (200.00±11.42), and total leukocyte count (7.44±0.02) compared to A. carolinianum (47.57%, 165.83±3.96, and 7.01±0.01, respectively). P. longiflora significantly reduced the percentage of leukocytes with depolarized mitochondria (3.24±0.16%) and apoptosis (1.81±0.07%), and induced a better CMI response than A. carolinianum. Significantly (p<0.05) higher hemagglutination titer (28.37±0.80) and IgG production (6.43±0.34mg/mL) were observed in the P. longiflora-treated group than in the A. carolinianum-treated group (23.93±0.58 and 6.23±0.37mg/mL). Plasma tumor necrosis factor-α (TNF-α) and TGF-ß1 levels, and nuclear factor-κB (NF-κB) expression were significantly (p<0.05) lower in the P. longiflora-treated group than in the A. carolinianum-treated group. This may be due to better HMI responses produced by P. longiflora than by A. carolinianum. This is the first study to show that P. longiflora ethanol extract has more potent in vitro and in vivo immunomodulatory activities than A. carolinianum, especially in alloxan-induced diabetic rats. However, further research is needed to identify the different molecular mechanisms involved in mediating this immunomodulatory response.

Fraxetin and ethyl acetate extract from Lawsonia inermis L. ameliorate oxidative stress in P. berghei infected mice by augmenting antioxidant defence system.

BACKGROUND: Lawsonia inermis L. is a well-documented plant for cosmetic as well as medicinal properties. It is used by local communities in India and Nigeria for the treatment of many parasitic diseases, including malaria. HYPOTHESIS/PURPOSE: Earlier studies on the plant's antiplasmodial activity were not assigned to any phytochemical with no quality assurance data. In this report, a recent chemically characterized extract and it's major constituent were investigated for in vitro antiplasmodial activity on chloroquine sensitive NF-54 strain. Furtherly, the potent extract and this constituent were assessed in vivo in Plasmodium berghei infected mice. The bioactive phytochemical and enriched extract were also monitored against various oxidative stress parameters. STUDY DESIGN/METHOD: The extract characterization was done by the quantitative analysis of eight phytochemicals using gradient reverse phase HPLC method. In vitro antiplasmodial activity was evaluated on chloroquine sensitive NF-54 strain by the determination of pfLDH activity. In vivo activity of the most potent extract and constituent were evaluated in P. berghei infected mice upon oral administration. The estimation of oxidative stress was done by monitoring various enzymatic and non-enzymatic parameters. RESULTS: The ethyl acetate extract of leaves (IC50 9.00 ±â€¯0.68 µg/ml) and fraxetin (IC50 19.21 ±â€¯1.04 µM) were the most effective in in vitro assays therefore selected for in vivo tests. The administration of the ethyl acetate extract of leaves and fraxetin to the infected mice resulted in significant (p < .05) suppression of parasitaemia as evidenced by a 70.44 ±â€¯2.58% to 78.77 ±â€¯3.43% reduction compared to non-infected group. In addition, a two-fold increase in mean survival time, a significant (p < .05) reduction in lipid peroxidation and an elevation in glutathione, catalase and superoxide dismutase were also observed in treated mice. The post-infection treatment also led to an augmentation of endogenous antioxidant enzymes (GST, GR, GPx) with respect to the infected control. A significant (p < .05) elevation in serum Nrf2-antioxidant response element level responsible for the activation of endogenous enzymes was also observed. CONCLUSION: It was evident from the experiments that ethyl acetate extract of L. inermis and fraxetin were able to suppress the oxidative damage by augmenting endogenous antioxidant system and thus ameliorated the plasmodium infection in mice.

Beneficial health applications and medicinal values of Pedicularis plants: A review.

Pedicularis plants (Orobanchaceae), popularly known as lousewort, are found in Asia, Europe, and North America, and have been used in Sowa-Rigpa, the Himalayan art of healing and a traditional system of medicine for treating various ailments in humans. A comprehensive compilation on this valuable medicinal plant is not available, however. The present extensive review provides insight into the salient medicinal properties of Pedicularis plants with respect to various health issues and diseases. Our previous studies on Pedicularis plants from the Changthang region of Ladakh (India) and research advances leading to new developments in this field have prompted this review. The information presented here has been compiled and analyzed from authenticated published resources available on Medline, Pubmed, Pubmed Central, Science Direct, and other scientific databases. The Pedicularis genus consists of approximately 600 species (83 of which are found in India), with commonly reported species being Pedicularis longiflora Rudolph, P. bicornuta Klotzsch, P. oederi Vahl, P. cheilanthifolia, and P. pectinata. The major phytoconstituents of the Pedicularis sp. are phenols, phenylethanoids, phenylpropanoids, flavonoids, iridoids, lignans, and alkaloids, among others. The existing literature highlights that these compounds possess antioxidant, immunomodulatory, anti-inflammatory, antidiabetic, antibacterial, antifungal, analgesic, antitumor, hepatoprotective, neuroprotective, muscle-relaxing, antifatigue, diuretic, antipyretic, antithrombus, antihemolysis, and DNA-repairing properties. This medicinal herb is used in the treatment of leucorrhoea, fevers, sterility, rheumatism, general debility, collapse, and urinary problems, and for revitalizing the blood circulation, improving digestion, and maintaining vitality. This review emphasizes the various medicinal aspects of Pedicularis sp. plants containing a variety of phytoconstituents. Besides phenols, terpenoids, flavonoids, lignans, tannins, iridoid, and phenylpropanoid glycosides are among the active constituents responsible for multiple health effects. However, further extensive research is required to characterize the various phytoconstituents of Pedicularis to explore their modes of action at a molecular level and identify other beneficial applications that can exploit the tremendous medicinal potential of this important herb.

Diarylheptanoids Rich Fraction of Alnus nepalensis Attenuates Malaria Pathogenesis: In-vitro and In-vivo Study.

Diarylheptanoids from Alnus nepalensis leaves have been reported for promising activity against filariasis, a mosquito-borne disease, and this has prompted us to investigate its anti-malarial and safety profile using in-vitro and in-vivo bioassays. A. nepalensis leaf extracts were tested in-vitro against chloroquine-sensitive Plasmodium falciparum NF54 by measuring the parasite specific lactate dehydrogenase activity. Among all, the chloroform extract (ANC) has shown promising anti-plasmodial activity (IC50 8.06 ± 0.26 µg/mL). HPLC analysis of ANC showed the presence of diarylheptanoids. Efficacy and safety of ANC were further validated in in-vivo system using Plasmodium berghei-induced malaria model and acute oral toxicity in mice. Malaria was induced by intra-peritoneal injection of P. berghei infected red blood cells to the female Balb/c mice. ANC was administered orally at doses of 100 and 300 mg/kg/day following Peter's 4 day suppression test. Oral administration of ANC showed significant reduction of parasitaemia and increase in mean survival time. It also attributed to inhibition of the parasite induced pro-inflammatory cytokines as well as afford to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. In-vivo safety evaluation study revealed that ANC is non-toxic at higher concentration. Copyright © 2016 John Wiley & Sons, Ltd.

Advances in Boerhaavia diffusa hairy root technology: a valuable pursuit for identifying strain sensitivity and up-scaling factors to refine metabolite yield and bioactivity potentials.

The present study reports the Agrobacterium rhizogenes-mediated hairy root induction in of an ethno-medicinally significant herb-Boerhaavia diffusa L., for elucidating the underlying competence regarding its biosynthetic (i.e. boeravinone B and eupalitin) and bioactivity (antibacterial, antioxidant and anti-inflammatory) potentials. Host plant-specific receptiveness towards A. rhizogenes strains and disparity in compatibility threshold of leaf and nodal explants were evident. Only leaf explants responded, attaining hairy root induction with the ATCC 15834 followed by A4 and SA79 strains in reducing order of transformation efficiency. The growth behaviours differed amongst independent rhizoclones, and two clones of A4 (RBH) and ATCC 15834 (RBT8) origin demonstrated higher growth potentials. Polymerase chain reaction amplification of rol genes confirmed their transformed nature. Optimization of the appropriate solvent and reverse phase high-performance liquid chromatography parameters relating to the targeted metabolite production in the selected RBH and RBT8 clones revealed higher accumulation of eupalitin with the RBH clone having the best result of 1.44 times greater yield over the control root. Compared to the selected rhizoclones, the control roots however showed higher boeravinone B content. Devising a modified "stirred-tank" reactor through equipping with marine impellers and ring spargers facilitated high-density RBH root biomass yield with 6.1-fold and 1.15-fold yield increment of the boeravinone B and eupalitin respectively compared to shake-flask cultures. Considering the control roots, the RBH clone revealed analogous antioxidant/antibacterial activities with improved anti-inflammatory potential. The hairy root mediated higher production of boeravinone B and eupalitin could be achieved for the first time in bioreactor.

Diarylheptanoids from Alnus nepalensis attenuates LPS-induced inflammation in macrophages and endotoxic shock in mice.

Diarylheptanoids, a group of plant secondary metabolites are increasingly recognized as potential therapeutic agents. The aim of study was to ascertain the anti-inflammatory profile of diarylheptanoids from Alnus nepalensis against lipopolysaccharide (LPS)-induced inflammation in macrophages and endotoxic shock in mice. Extracts prepared from dried leaves of A. nepalensis using standard solvents were tested against LPS-induced inflammation in macrophages. Among all, butanol extract (ANB) has shown most significant inhibition of pro-inflammatory cytokines without any cytotoxicity. HPLC analysis of ANB showed the presence of diarylheptanoids. The diarylheptanoids were further isolated and tested in-vitro for anti-inflammatory activity. Treatment of isolated diarylheptanoids (HOG, ORE and PLS) was able to reduce the production and mRNA level of pro-inflammatory cytokines (TNF-α and IL-6). Furthermore, we demonstrated that it inhibited the expression of NF-kB protein in LPS-induced inflammation in macrophages. In-vivo efficacy and safety profile of ANB revealed that oral treatment of ANB was able to improve the survival rate, and inhibited the production of pro-inflammatory cytokines in serum, attenuated vital organ injury in a dose dependent manner without any toxic effect at higher dose in mice. The results suggest that diarylheptanoids from A. nepalensis can be considered as potential therapeutic candidates for the management of inflammation related diseases.

Flavonoids rich fraction of Citrus limetta fruit peels reduces proinflammatory cytokine production and attenuates malaria pathogenesis.

Exploration of possible pharmacological effects along with characterisation of the bioactive compounds present in peels may have a key role in converting the fruit waste materials into therapeutic value added products. Extracts prepared from the Citrus limetta fruit peels were studied for antioxidant and anti- inflammatory activity using in-vitro bioassays. Among all, ClEt an ethanol extract of Citrus limetta fruit peels has shown promising anti-oxidant and anti-inflammatory activity. ClEt was further validated to ensure its safety evaluation at 2000mg/kg and anti-malarial efficacy at 100, 250, 500 mg/kg body weight with special reference to inflammatory mediators involved in malaria pathogenesis. In-vivo study revealed that ClEt was safe at higher dose and showed promising anti-malarial activity by inhibiting the parasitaemia and inflammatory mediators (IFN-γ, TNF-α, IL-6) involved in malaria pathogenesis, able to improve the haemoglobin and glucose level and increase the survival time. Chemical fingerprint of ClEt revealed the presence of flavonoids. Results suggested the suitability of ClEt, a flavonoid rich fraction of Citrus limetta fruit peels as a candidate for further investigation towards the management of malaria pathogenesis.