Safety and Effectiveness of Liv.52 DS in Patients With Varied Hepatic Disorders: An Open-Label, Multi-centre, Phase IV Study.

Background The hepatoprotective function of polyherbal formulation Liv.52 in chronic liver diseases is well recognized in published literature. The objective of this open-label, phase IV study was to further strengthen and validate its safety and effectiveness using a large patient pool in a real-world scenario and provide scientific data on symptomatic improvement and supportive treatment in liver function with improvement in quality of life. Methods Adult patients of either sex with one or more clinical symptoms like fatigue, nausea, anorexia, abdominal pain or discomfort, muscle cramps, jaundice, or any other signs and symptoms with a history suggestive of mild-to-moderate hepatic disorders like alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), drug-induced hepatotoxicity, or hepatitis were treated with two Liv.52 DS tablets (oral) twice daily for 12 weeks. Results Out of the 1000 enrolled patients, 962 (96%) completed the study with the following subgroups ALD: 375 (38.9%), NAFLD: 379 (39.3%), drug-induced hepatotoxicity: 78 (8.1%), hepatitis: 130 (13.5%). The mean age of enrolled patients was 37.7 years, and the majority of them, 785 (78.5%) were men. The common adverse events observed (with >1.5% incidence) in the study were abdominal pain: 26 (2.6%) and headache: 17 (1.7%). Liv.52 showed statistically significant improvement (P<0.0001) in various clinical signs and symptoms in the majority of patients namely, fatigue: 357/723 (49%), anorexia: 485/620 (78.2%), jaundice: 48/52 (92%). Majority of the patients showed significant improvements from baseline to end of 12 weeks in the liver function test parameters namely, aspartate aminotransferase: 633/840 (75.36%), alanine aminotransferase: 592/729 (81.21%), serum bilirubin: 244/347 (70.32%), alkaline phosphatase: 279/355 (78.59%) with P<0.0001 for all parameters. Statistically significant improvement (P<0.005) was also seen in all the components of the chronic liver disease questionnaire (CLDQ) scores from baseline to 12 weeks. Conclusions The study demonstrated that Liv.52 was hepatoprotective and well tolerated in the study population after treatment for 12 weeks. Significant improvements were seen in clinical signs and symptoms, laboratory parameters of liver function, and CLDQ scores from baseline to 12 weeks. No significant or new safety signals emerged from this study.

In vitro immuno-stimulatory and anticancer activities of Oroxylum indicum (L.) Kurz.: An evidence for substitution of aerial parts for conservation.

BACKGROUND: In Ayurveda, "Dashamoolarishta" is one of the important composite herbal formulations. Mainly, the root and root bark of Oroxylum indicum are used as one of the ingredients in its preparation. This leads to over exploitation of medicinal plants owing, to excessive demand due to population expansion and its perceived importance in traditional herbal remedies. OBJECTIVE: For the conservation of biodiversity, the present investigation had an objective to prepare the extracts of different parts of O. indicum plant and to, compare the chemo-profiles as well as to study the biological activities of the prepared extracts. MATERIALS AND METHODS: Hydro-alcoholic (HA) and aqueous (Aq) extracts of various plant parts were prepared and chemical investigation was done with the help of (LC-MS/MS). Further, in vitro biological activities such as immuno-stimulation (IS) using a cytokine bioassay in RAW264.7 and in vitro anticancer in TNF-α ELISA in THP-1 cells were studied. RESULTS: The mass spectral profile of the plant revealed the presence of markers such as oroxylin A and chrysin in HA and Aq extracts of stem, leaf, bark and root. Cytokine release and TNF-α secretion was observed in both hydro-alcoholic and aqueous extracts. CONCLUSION: Based on the results from the present study, it can be concluded that it is possible to replace the roots and the bark of O. indicum with the stem of young plants and leaves. It paves a way for the conserving the medicinal plants without uprooting and extinguishing the whole plant.

Ketosteroid Standardized Cissus quadrangularis L. Extract and its Anabolic Activity: Time to Look Beyond Ketosteroid?

BACKGROUND: Cissus quadrangularis (CQ) L. reported to contain 3-ketosteroids and have bone health benefits. AIM: This study aimed at establishing the relationship between the ketosteroid content and anabolic as well as bone health-promoting activities of various Cissus extracts in well-established orchidectomized (ORX) rat model. MATERIALS AND METHODS: Supercritical carbon dioxide, ethyl acetate, and aqueous extracts (AE) of CQ L. were prepared and standardized for ketosteroid content by two methods used in commerce. Moreover, ketosteroid standardized extracts of this plant were evaluated for anabolic activity in rats in well-established ORX rat model. RESULTS: The increase in the absolute weight was appreciable in the CQ-AE treated group. Similarly, with respect to bone parameters, a similar trend was seen. The mean bone density, strength, and calcium content were found to be highest in the group treated with CQ-AE compared to groups treated with other extracts. This study reveals for the first time that 3-ketosteroids are not linked to the beneficial activities on bone and highlights the need for extensive characterization of biological active principles from CQ L. CONCLUSION: In light of the above estimation studies, we believe that current standardization of Cissus extraction "3-ketosteroids" is incorrect. We also did not find any report suggesting the presence of androgenic steroids in this plant and hence the characterization based on "3-ketosteroids" is scientifically incorrect. This study highlights the insufficient understanding of biological active principles from CQ L. and underlines the need for extensive bioactivity guided studies. SUMMARY: Cissus quadrangularis (CQ) L. reported to contain 3.ketosteroids and have bone health benefitsWe did not find correlation between ketosteroid content obtained by conventional methods and its biological effectStudies indicate that claims of ketosteroid content need not necessarily correlate to biological effects and hence warrants extensive phytochemical characterization of biological active principles from CQ L. Abbreviations used: CQ: Cissus quadrangularis, ORX: Orchidectomized, AE: Aqueous extract, EE: Ethyl acetate extract, SFE: Supercritical fluid extract.

Anti-skin ageing activity of napthoquinones from Arnebia nobilis Reichb.f.

The present isolation and identification of napthoquinones from roots of Arnebia nobilis Reichb.f. can lead to the discovery of new anti-skin ageing ingredient in colour cosmetics. Four compounds have been isolated and purified by rigorous column chromatography. The compounds are identified as ß, ß-dimethylacryl alkannin (AN-I), acetoxyisovaleryl alkannin (AAN-II), acetyl alkannin (AN-III) and alkannin (AN-IV) by interpretation of spectroscopic data. This study is the first to report the isolation of Acetoxyisovaleryl alkannin (AAN-II) from A. nobilis. The IC50 values of the compounds, determined in human skin cells (human dermal fibroblasts and human keratinocytes) and mouse embryonic fibroblasts (NIH3T3) varied significantly among the four alkannins. Among the four compounds, ß-acetoxyisovaleryl alkannin (AAN-II) significantly inhibited hydrogen peroxide (H2O2)-induced red blood corpuscle haemolysis and cellular senescence in human dermal fibroblasts. Collagen-I, elastin and involucrin syntheses in human dermal fibroblasts or keratinocytes were up regulated by AAN-II. These results support the potential utility of alkannins as novel anti-ageing ingredients.

A contemporary approach on design, development, and evaluation of Ayurvedic formulation - Triphala Guggulu.

INTRODUCTION: Ayurvedic texts describe many formulations for different ailments. Triphala Guggulu (TG) is reputed for treating inflammatory conditions. These formulations have been considered complementary medicine or alternative to conventional medicines across the globe. These complex polyherbal formulations need science-based approach toward manufacturing process and chemical standardization. AIM: To evaluate TG tablets to meet modern pharmaceutical approaches and also standardization processes. MATERIALS AND METHODS: Shodhana of Guggulu was performed using Triphala Kwatha (decoction) as mentioned in ayurvedic texts. This processed material was dried using spray drying technique, blended with other herbal powders as per formula and using suitable excipients was incorporated for compressing into tablets. Excipients and their concentrations were evaluated for various micromeritic properties and the formula that met the requirements was compressed. RESULTS: The angle of repose was considered fair with a range of 25-30, Carr's index at a range between 17 and 30, and Hausner ratio of 1.21:1.44, which was well within the limits as per the United States Pharmacopeia (USP) and among the three blends tested, blend Triphala Guggulu formulation-3 was found most suitable for tablets compression. Physical properties were well within the limits as per the USP and disintegration time was within 30 min. CONCLUSION: Modern pharmaceutical processing can very well be adapted for Guggulu preparations.

Hydnocarpus: an ethnopharmacological, phytochemical and pharmacological review.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Hydnocarpus (Flacourtiaceae) includes forty species that are spread across the globe. In the Indian System of Medicine, Hydnocarpus pentandrus (Buch.-Ham.) Oken. is primarily used for treating leprosy and other skin disorders. It is known as "Chaulmoogra" and is also used to treat other indications including constipation, inflammation, blood disorders, and worm infestations. Various species of Hydnocarpus are also used in traditional medicine in China, Thailand, Malaysia, and Myanmar for several skin disorders. To assess the therapeutic potential of species from the Hydnocarpus genus and to determine future avenues for research. METHODS: All relevant scientific literature published up to the end of December 2013 was retrieved via a library and electronic search (SciFinder, PubMed, ScienceDirect, and Google Scholar). Manual searches of traditional books like to ancient classics, including Vaidya Yoga Ratnavali, Siddha Materia Medica, and contemporary references including The Ayurvedic Pharmacopoeia of India and The Ayurveda Formulary, were also performed. RESULTS: Seed oil from species of the Hydnocarpus genus is used for medicinal purposes, predominantly for various skin disorders. This oil is reported to contain a characteristic class of compounds known as cyclopentenyl fatty acids. Furthermore, seeds of this genus are reported to contain triglycerides of fatty acids, sterols, flavonoids, and flavonolignans. Hydnocarpin, a flavonolignan, is reported to potentiate antimicrobial and anticancer activity. The extracts and compounds isolated from this plant show a wide spectrum of pharmacological properties, including antibacterial, antileprotic, antitubercular, antipsoriatic, antirheumatic, hypolipidemic, antidiabetic, anticancer, anti-inflammatory, and antioxidant activities. The antileprotic activity is postulated to be due to the cyclopentenyl fatty acids present in the seed oil. CONCLUSION: Flavonolignans have an interesting chemical motif, and hydnocarpin and its congeners should be investigated for their activities and the mechanism underlying these activities. Multi-drug-resistant microbes are on the increase, and the possible inhibitory effect of these compounds when used with current antimicrobials should also be evaluated. Furthermore, unique cyclopentenyl fatty acids should also be investigated to understand the exact mechanism of action underlying antileprotic activity. Additional in depth phytochemical investigations of seed oil and extracts are required to tap the true potential of species from the Hydnocarpus genus.

Assessment of inhibitory potential of Pothos scandens L. on ovalbumin-induced airway hyperresponsiveness in balb/c mice.

Pothos scandens L. was used in Indian traditional medicine as an antiasthmatic drug. The ethanolic and aqueous extracts were prepared with aerial parts of P. scandens (PSE & PSA). ESI MS/MS of PSE ethanolic extract was carried out for the determination of chemical constituents. CP1 is isolated from the PSE, structurally confirmed with NMR and LCMS/MS. PSE, PSA and CP1 are evaluated against ovalbumin (OVA) induced airway hyperresponsiveness (AHR) in balb/c mice. The test drugs are administered p.o. prior to challenge with aerosolized 2.5% w/v OVA. Total and differential leucocyte count, nitrite (NO2), nitrate (NO3), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-13 (IL-13) are estimated in bronchoalveolar lavage fluid (BALF). Similarly, myeloperoxidase (MPO), malonaldehyde (MDA) and total lung protein (TLP) are estimated in the lungs. The results reveal a significant increase in total and differential leucocyte count, NO2, NO3, TNF-α, IL-6, and IL-13 in OVA induced AHR. However, these parameters are significantly decreased in PSE and PSA tested doses (PSE 100 & 200mg/kg). While, treatment with CP1 is less effective at 5 & 10mg/kg doses. Similar observations obtain for MPO and MDA in lungs. However, the mean value indicated that the PSE at 200mg/kg showed a significant restoration in all the parameters. Pro-inflammatory mediators are known to be responsible for AHR. Histopathology revealed justifies the effectiveness. The present investigations suggest PSE are interesting molecules for further research for asthma, with an approach through pro-inflammatory inhibitory pathway. P. scandens is a potential herbal medicine for allergy induced asthma.

Identity and pharmacognosy of Ruta graveolens Linn.

Ruta graveolens L., is a odoriferous herb belonging to the family Rutaceae. It is the source of Rue or Rue oil, called as Sadab or Satab in Hindi. It is distributed throughout the world and cultivated as a medicinal and ornamental herb. The ancient Greeks and Romans, held the plant in high esteem. It is used in Ayurveda, Homoeopathy and Unani. Phytochemical constituents and pharmacological properties were studied in depth. In 14 species of genus Ruta, R. graveolens and R. chalepensis are available in India and also cultivated in gardens. Taxonomical characters to identify the Indian plants are very clear with fringed and or non-fringed petals. However, references to it are confused in the traditional literature. Due to sharing of regional language name, its identity is confused with Euphorbia dracunculoides. Morphological and anatomical characters were described. Pharmacognostic studies with microscopic characters were also published. Upon reviewing the anatomical characters and pharmacognostic characters one finds that it is highly confused and conflicting. The characters described are opposite of each other and authenticity of the market sample of R. graveolens cannot be guaranteed and able to be differentiated from R. chalepensis. Present work is to describe the pharmacognostic characters of R. graveolens to differentiate it from R. chalepensis. It is concluded that morphologically, R. graveolens can be identified with its non-fringed petals and blunted apices of fruit lobes. Whereas, in R. chalepensis petals are fringed or ciliated and apices of the fruit lobes are sharp and projected. Microscopically, in stem of R. graveolens pericyclic fibers have wide lumen. Whereas, in R. chalepensis, it is narrow. The published pharmacognosy reports do not pertain to authentic plant or some of the characteristic features like glandular trichomes are not observed in our samples.

Botanical pharmacognosy of stem of Gmelina asiatica Linn.

Gmelina asiatica Linn (G. parvifolia Roxb.) is a large shrub or a small tree. Roots and aerial parts are used in Ayurvedic medicine and also have ethno-medical uses. Root is reported as adulterant to G. arborea roxb roots. Pharmacognostical characters of root were reported. Owing to the shortage of genuine drug and ever-increasing demands in market, it becomes necessary to search an alternative with equal efficacy without compromising the therapeutic value. Nowadays, it becomes a common practice of using stem. In case of roots phytochemical and pharmacological analysis of stem was reported. However, there is no report on the pharmacognostical characters of stem and to differentiate it from roots. The present report describes the botanical pharmacognostical characters of stem and a note to differentiate it from root. Hollow pith, faint annual rings in cut ends, alternatively arranged macrosclereids and bundle cap fibers, and presence of abundant starch grains and calcium oxalates in pith and in ray cells are the diagnostic microscopic characters of stem. Stem pieces can be differentiated from roots by absence of tylosis.

Pharmacognostical Studies on Balanophora fungosa - a Negative Listed Plant.

Balanophora fungosa Forster & Forster ssp. indica (Arn.) B. Hansen var. indica, (Balanophoraceae) syn. B. indica, is a root parasite found in hills of south India. This plant is included in the list of negative list, which are restricted and prohibited for export. Though it is not an official drug in any of the indigenous systems of medicine in India, it is used in tribal medicines in south India. However, it is found in crude drug markets as substitute/adulterant for the Ayurvedic drug Gajapippali (Scindapsus officinalis). Few phytochemical constituents were reported on this plant. However, there is no pharmacognostical report to authenticate the commercial samples of B. fungosa and to differentiate them from Scindapsus officinalis. This article describes the pharmacognostical characteristics of Balanophora fungosa and diagnostic features to differentiate it from Scindapsus officinalis.

NCB-02 (standardized Curcumin preparation) protects dinitrochlorobenzene- induced colitis through down-regulation of NFkappa-B and iNOS.

AIM: To evaluate the efficacy and mechanism of action of NCB 02, a standardized Curcumin preparation, against 2, 4 dinitrochlorobenzene (DNCB) induced ulcerative colitis in rats. METHODS: Ulcerative colitis was induced in male rats by sensitizing with topical application of DNCB in acetone for 14 d and intra-colonol challenge with DNCB on day 15. A separate group of animals with vehicle treatment in similar fashion served as control group. Colitis rats were divided into different groups and treated with NCB-02 at doses of 25, 50 and 100 mg/kg b.wt p.o. for 10 d. Sulfasalazine at a dose of 100 mg/kg b.wt for 10 d served as a reference group. On day 10 after respective assigned treatment, all the animals were euthanized and the length of the colon, weight of entire colon and distal 8 cm of the colon were recorded. The distal part of the colon was immediately observed under a stereomicroscope and the degree of damage was scored. Further distal 8 cm of the colon was subject to the determination of colonic myeloperoxidase (MPO), lipid peroxidation (LPO) and alkaline phosphatase (ALP) activities. A small piece of the sample from distal colon of each animal was fixed in 10% neutral buffered formalin and embedded in paraffin wax and sectioned for immunohistochemical examination of NFkappa-B and iNOS expression. RESULTS: NCB-02 showed a dose dependent protection against DNCB-induced alteration in colon length and weight. NCB-02 treatment also showed a dose dependent protection against the elevated levels of MPO, LPO and ALP, induced by DNCB. NCB-02 demonstrated a significant effect at a dose of 100 mg/kg b.wt., which was almost equipotent to 100 mg/kg b.wt. of sulfasalazine. Treatment with sulfasalazine and curcumin at a dose of 100 mg/kg b.wt. inhibited the DNCB-induced overexpression of NFkappa-B and iNOS in the colon. CONCLUSION: Curcumin treatment ameliorates colonic damage in DNCB induced colitic rats, an effect associated with an improvement in intestinal oxidative stress and downregulation of colonic NFkappa-B and iNOS expression.

Constituents of Carapa granatum fruits.

The isolation of 6alpha,11beta-diacetoxygedunin (1) and other minor constituents from Carapa granatum fruits is reported.