Ayurvedic drug induced liver injury

Drug induced liver injury is responsible for 50% of acute liver failure in developed countries. Ayurvedic and homeopathic medicine have been linked to liver injury. This case describes the first documented case of Punarnava mandur and Kanchnar guggulu causing drug induced liver injury. Drug induced liver injury may be difficult to diagnosis, but use of multi-modalities tools including the ACG algorithms, causative assessment scales, histological findings, and imaging, is recommended. Advanced imaging, such as magnetic resonance cholangiopancreatography, may possibly have a greater role than previously reported in literature.

Immunopotentiality of Ayurvedic polyherbal formulations “Saribadi” and “Anantamul Salsa” with augmentation of IgM production and lymphocytes proliferation:A preliminary study

Objective:To assess the immunopotentiality of Ayurvedic polyherbal preparations,"Saribadi" and "Anantamul Salsa".Methods: Freshly prepared BALB/c mice splenocytes were cultured with "Saribadi" or"Anantamul Salsa" treatment [doses of 0.25%, 0.50%, 0.75%, 1.00%, 1.50%, 2.00%,3.00% and 4.00%(v/v)] at 37C for 5 days. The immunoglobulin M(IgM) production and lymphocytes proliferation were determined by ELISA and MTT methods, respectively.Endotoxin contamination was assessed by treating the preparations with polymyxin B.Results: The doses of "Saribadi" [0.25%, 0.50%, 0.75% and 1.00%(v/v)] significantly increased IgM productions(0.966, 0.728, 0.695 and 0.615 mg/m L vs. control 0.265 mg/m L)and lymphocytes proliferation [absorbance 0.311, 0.394, 0.372 and 0.334 optical density(OD) vs. control 0.162 OD]. Similarly, the doses of "Anantamul Salsa" [0.50%, 0.75%,1.00% and 1.50%(v/v)] promoted IgM productions(0.933, 0.919, 0.917 and 0.892 mg/m L vs. control 0.502 mg/m L) and the doses of "Anantamul Salsa" [0.50%, 0.75%, 1.00%,1.50%, 2.00%, and 3.00%(v/v)] stimulated lymphocytes proliferation(absorbance 0.395,0.326, 0.440, 0.398, 0.452 and 0.355 OD vs. control 0.199 OD). The activity of "Saribadi"and "Anantamul Salsa" was not retarded by the treatment of preparations with polymyxin B.Conclusions: Immunomodulatory activity of "Saribadi" and "Anantamul Salsa" was unveiled for the first time. "Saribadi" and "Anantamul Salsa" possess immunostimulating potential acting through the induction of lymphocyte proliferation and IgM production.These preparations may be useful in strengthening immune responses. However, further cellular and in vivo studies are required.

Exercise-induced anaphylaxis with an Ayurvedic drug as cofactor:A case report

BACKGROUND The practice of Indian Ayurvedic medicine is spreading in Western countries and Shilajit is one of the most used drugs, for its antioxidant activities and immunomodulatory effects. Albeit Shilajit has showed a high degree of safety, it can act as cofactor of anaphylaxis, especially in condition at high risk, such as mast cell activation syndrome(MCAS). We reported this case to sensitize practitioners to investigate to the use of complementary and alternative medicine,in case of exercise-induced anaphylaxis(EIAn).CASE SUMMARY A 43-year-old woman, working as a dance teacher, developed urticaria after ingestion of rice, tuna and Shilajit, which did not respond to intramuscular corticosteroids. Subsequently, she developed dyspnoea and hypotension with loss of consciousness that arose 1 h after sexual activity. The patient did not refer personal history of atopy. Specific IgE for main food allergens resulted negative,with total IgE levels of 14 IU/L. Oral provocation test with Shilajit was not perfomed because the patient refused, but we performed prick-by-prick and patch test that resulted negative. Serum tryptase at the time of anaphylaxis was 20.6 μg/L that fell down to of 10.6 μg/L after therapy, but has remained at the high value after two days and during the follow-up. We performed an analysis of the c-KIT gene in peripheral blood, which was negative. We felt the diagnosis consistent with EIAn in a patient with a possible MCAS.CONCLUSION In Western countries the use of drugs from Ayurvedic medicine is more common than in the past. These substances can be cofactors of anaphylaxis in patients with risk factors.

Formulation of Ayurvedic Medicines and Extracts of Medicinal Plants as an Alternative Therapeutic Treatment Option for Nephrolithiasis

The incidence of nephrolithiasis,commonly known as kidney stone,is increasing worldwide with significant health and economic burden.Approximately 2 million people every year in India are affected by kidney stones.It affects all ages,genders,and races,but between the ages of 20 and 49 years,it affects most frequently in men than women.Different types of stones include calcium stones,cysteine stones,struvite or magnesium ammonium phosphate stones,uric acid stones,and drug-induced stones.This review article provides information about general pathophysiology,epidemiology,clinical presentation,and pharmacological treatment,which includes ayurvedic and herbal medicines for nephrolithiasis.Further understanding of the pathophysiological link between nephrolithiasis and systemic disorders is necessary for the development of new therapeutic options.

The Current Acceptance,Accessibility and Recognition of Chinese and Ayurvedic Medicine in the United States in the Public,Governmental,and Industrial Sectors

To assess the current level of acceptance in the United States of complementary and alternative medicine, recent research into the prevalence, acceptance, accessibility, and recognition of complementary and alternative therapies were reviewed. Several signs point to an increasing acceptance of complementary and alternative medicine in the United States; the use of complementary and alternative medicine is significantly increasing, many aspects of Chinese medicine and Ayurveda are becoming mainstream, practitioners in the United States are beginning to be licensed, and insurance companies are beginning to cover some complementary and alternative therapies. Remaining challenges to true acceptance include the restrictive Western mindset, the absence of published studies, a lack of consistent manufacturing processes and quality standards, and a fear of adulteration. Although the field still faces many challenges, alternative and complementarymedicine, including Chinese medicine and Ayurvedic medicine, is becoming more accepted and accessible in the United States.

Ayurvedic concept of Shatkriyakala:a traditional knowledge of cancer pathogenesis and therapy

The term Kriyakala refers to the recognition of the stage of a disease＇s progress, which helps to determine appropriate measure to correct the imbalance in Doshas （biological factors）. It is a compound expression, comprised of Kriya and Kala, where Kriya means the choice to treatment （medicine, food and daily-routine） used to improve the disturbance in Doshas, and Kala refers to the stage of progress of a disease. Sushruta, an ancient Indian surgeon, has described the concept of Kriyakala in Vamaprashnadhyaya, an ancient Vedic Sanskrit text, which seeks to explain the incidence of Vamas in terms of Doshic disturbances. Vama, in modern parlance, may be described as an inflammatory process that may lead ulceration and chronic inflammation, promoting all stages of carcinogenesis. Abnormal interactions between Prakriti （genotype） and environmental factors vitiate the Doshas and impair immunity, which can lead to aberrant cell growth and cancer. Moreover, the interaction between vitiated Doshas and weak Dhatus （body tissues） manifests as cancers of a specific organ. Shatkriyakala （six stages of progress of a disease）, on the other hand, provides a framework to assess the cancer and its pathogenesis in different stages. According to Ayurvedic concepts, all cancer therapies treat the affected tissues indirectly by eliminating vitiated Doshas, rejuvenating Dhatus and restoring immunity in cancer patients. The present review describes the six stages of Shatkriyakala in detail, with an emphasis on research areas to validate the concept of Shatkriyakala. This traditional knowledge can be utilized with modern technologies to detect predisposition for cancer or diagnose cancer in its early stages.

Chyawanprash,a formulation of traditional Ayurvedic medicine,shows a protective effect on skin photoaging in hairless mice

OBJECTIVE： Chronic exposure to ultraviolet （UV） radiation induces skin photoaging （premature skin aging）. UV irradiation generates reactive oxygen species （ROS）, which are shown to play a pivotal role in skin photoaging. Ayurveda is a holistic traditional medical system, and Chyawanprash is one of the most popular formulations in Ayurveda. Since maintenance of the function and appearance of skin is important, we examined whether Chyawanprash has a protective effect on skin photoaging. METHODS： To examine the effect of Chyawanprash on skin photoaging, hairless mice were administered with Chyawanprash in drinking water for 3 weeks, and then repeatedly exposed to ultraviolet light B （UVB） irradiation （225 or 450 mJ/cm2） to induce skin photoaging. To further examine the function of Chyawanprash, its effects were examined in cells cultured in vitro. Chyawanprash was added in culture medium, and examined for the effect on the growth of human keratinocytes, and for the ability to eliminate ROS which generated by paraquat （50 μmol/L） in HeLa cells. RESULTS： UVB irradiation caused symptoms such as rough skin, erythema, and edema on the skin in hairless mice, but administration of Chyawanprash relieved these symptoms. Further, Chyawanprash significantly suppressed epidermal thickening, a typical marker of skin photoaging, in mice. We then analyzed the effect of Chyawanprash in human cells in culture, and found that Chyawanprash enhanced the growth of human keratinocytes, and efficiently eliminated ROS, which are causally involved in skin photoaging, in HeLa cells. CONCLUSION： These findings suggested that Chyawanprash may have beneficial effects on slowing skin photoaging.

Status of Indian medicinal plants in the International Union for Conservation of Nature and the future of Ayurvedic drugs: Shouldn’t think about Ayurvedic fundamentals?

The present market for herbal drugs is estimated about ?40 billion, which is expected to increase by 16% in next 3-4 years. The current production of many Ayurvedic herbs is less than their market demand, which incentivizes adulteration in the Ayurvedic drug supply chain. The present work aims to highlight the most used Ayurvedic plants that have been listed in the International Union for Conservation of Nature's "red list" of endangered or vulnerable plants. The future of Ayurvedic medicines from these listed plants is uncertain, as the collection of herbs from their natural habitat is prohibited and their cultivation does not meet market demands. Many of these plants, such as Taxus baccata and T. wallichiana, are endangered and are only grown in their natural habitats;their cultivation in other areas is impractical. This is the present state, and will worsen as demand continues to grow, with increasing populations and increasing adoption of this system of medicine. It is possible that in coming years most of the Ayurvedic drugs will be adulterated, and will cause only side effects rather than the therapeutic effects. The Ayurvedic fundamentals are under-explored areas where the Ayurvedic practitioners and research scientists can work together. The scientific work on the basic principles will unravel many unknown or little-known facts of this ancient science. Hence, the present review emphasizes the conservation of Ayurvedic herbs, minimization of the use of medicinal plants and the promotion of the research based on Ayurvedic fundamentals.

Studies on metals and pesticide content in some Ayurvedic formulations containing Bacopa monnieri L.

OBJECTIVE： Ayurvedic formulations are preferred over other formulations as well as commercialized on broad level to treat various ailments. The World Health Organization has established certain guidelines for quality control of heavy metals and pesticide residues. Bacopa monnieri, a popular herb with immunomodulator and memory-enhancing properties is the chief constituent of several Ayurvedic formulations, which include Brahmi Vati （BV）, Brahmi Ghrita （BG） and Saraswat Churna （SC）, etc. In view of the World Health Organization guidelines, two products of each formulation from six different manufacturers were purchased from Ayurvedic Pharmacy, Bulanala-Varanasi, India for testing heavy metal and pesticide residue. METHODS： In the present study, all the formulations--BY, BG and SC--were selected for estimation of four heavy metals namely lead （Pb）, cadmium （Cd）, chromium （Cr） and nickel （Ni） by a plasma emission spectrophotometer. Organochlorine pesticidal residues were estimated for dichlorodiphenyl trichloroethane, isomers of hexachlorocyclohexane （HCH） and a-endosulfan, etc. in total 12 samples of test formulations containing Bacopa monnieri L. using gas chromatography technique. RESULTS： Out of 12 samples, Pb, Cd, Cr and Ni were present in all samples but below the permissible limit. Although atrazine, aldrin, dialdrin were in below detection limit, but other pesticides were detected in some samples as oxamyl, hexachlorocyclohexanes （α-HCH, β-HCH and y-HCH）, dichlorodiphenyl trichloroethane and dichlorodiphenyl dichloroethylene. CONCLUSION： The presence of heavy metals in evaluation of heavy metals and pesticide residue the formulations was low to cause toxicity. However n every batch is necessary.

Medicinal values of aquatic plant genus Nymphoides grown in Asia: A review

Nymphoides is an aquatic genus consisting about 50 species, of which few were accepted as traditional medicinal plants in Asia. The literature review revealed that Nymphoides species are widely used in Ayurvedic medicine as a popular drug, i.e. Tagara. They are also utilized by the traditional local healers of different Asian countries to treat various diseases, like convulsion, jaundice, fever, headache, etc. According to the in vivo and in vitro pharmacological studies, Nymphoides species have been claimed to possess major biological activities like anticonvulsant, antioxidant, hepatoprotective, cytotoxic, antitumor, etc. Biochemical profiling of different aquatic plants of this genus revealed the presence of some important phytochemicals as polyphenolic component, flavonoids, triterpenes, carbohydrates, glycosides, etc. Several valuable bioactive compounds including ephedrine, coumarin, secoiridoid glucosides, methyl quercetin, ferulic acid, foliamenthoic acid, etc. were also known to be isolated and identified from different Nymphoides species. The aim of this review is to analyze the published report based on the medicinal values of different Asian Nymphoides species, to provide the updated information about the ethnomedicinal, pharmacological as well as the phytochemical properties for the first time.

A Strategy to Employ Clitoria ternatea as a Prospective Brain Drug Confronting Monoamine Oxidase (MAO) Against Neurodegenerative Diseases and Depression

Ayurveda is a renowned traditional medicine practiced in India from ancient times and Clitoria ternatea is one such prospective medicinal herb incorporated as an essential constituent in a brain tonic called as medhya rasayan for treating neurological disorders.This work emphasises the significance of the plant as a brain drug there by upholding Indian medicine.The phytochemicals from the root extract were extricated using gas chromatography–mass spectrometry assay and molecular docking against the protein Monoamine oxidase was performed with four potential compounds along with four reference compounds of the plant.This persuades the prospect of C.ternatea as a remedy for neurodegenerative diseases and depression.The in silico assay enumerates that a major compound(Z)-9,17-octadecadienal obtained from the chromatogram with a elevated retention time of 32.99 furnished a minimum binding affinity energy value of-6.5 kcal/mol against monoamine oxidase(MAO-A).The interactions with the amino acid residues ALA 68,TYR 60 and TYR 69 were analogous to the reference compound kaempferol-3-monoglucoside with a least score of-13.90/-12.95 kcal/mol against the isoforms(MAO)A and B.This study fortifies the phytocompounds of C.ternatea as MAO-inhibitors and to acquire a pharmaceutical approach in rejuvenating Ayurvedic medicine.

Nootropic Activity of <i>Caralluma fimbriata</i>Extract in Mice

We investigated the effects of a standardized extract of Caralluma fimbriata Wall (CFE) on learning and memory in mice using various behavioural models. Unusually, CFE exerts both nootropic and anxiolytic effects.

Development of Commonsense Knowledge Modeling System for Psychological Assessment in Clinical Psycho

According to the Buddhist philosophy, hatred （dosa） is considered as one of the three unwholesome roots which determine the actual immoral quality of volitional states and a conscious thought with its mental factors. Hatred, then, comprises all degrees of repulsion from the faintest trace of ill-humour up to the highest pitch of hate and wrath. Thus, ill-will, evil intention, wickedness, corruption and malice are various expressions and degrees ofdosa. A hateful temperament is said to be due to a predominance of the type of dosa, apo, vayu and semha. Vedic psychology forms the clinical core of mental health counseling in the Ayurvedic medical tradition. According to Ayurvedic medical practises, a person is dominated on one of constitutes type （type ofdosa） namely vata （vayu）, pita （apo） or kapha （semha）. This is known as prakurthi pariksha. Important aspect of identification of constitute type is for diagnosis of mental diseases, because each of constituent type has a list of probable mental diseases. An important area of expertise for many clinical psychologists is psychological assessment. Constructions of information systems using psychological assessment in clinical psychology have a problem of effective communication because of implicit knowledge. This complicates the effective communication of clinical data to the psychologist. In this paper, it presents an approach to modeling commonsense knowledge in clinical psychology in Ayurvedic medicine. It gives three-phase an approach for modeling commonsense knowledge in psychological assessment which enables holistic approach for clinical psychology. Evaluation of the system has shown 77% accuracy.

Pharmacodynamic evaluation for antiplasmodial activity of Holarrhena antidysentrica(Kutaja) and Azadirachta indica(Neemb) in Plasmodium berghei infected mice model

Objective:To investigate in-vivo anti-plasmodial activity of aqueous extracts of plants selected based on the symptomology mentioned in Ayurveda.Methods:The aqueous extracts of Holarrhena antidysentrica(H.antidysentrica)(Kutaja) and Azadirachta indica(A.indica)(Neemb) for their antiplasmodial potential in Plasmodium berghei(P.berghei) infected mice was assessed using Peters four day suppressive test.Both the extracts were administered at 2 dose levels,full dose(1 000 mg/d) and minimized dose(200 mg/d).10~6 P.berghei infected RBCs were injected on day ’0’ and treated from day ’0’ till day ’3’ post-infection,Tail blood smears were collected, giemsa stained and analyzed.The mice were observed for survival and parasitemia was assessed till 50%of mice in control survived.Results:It was observed that the percentage of parasitemia increased gradually in all the groups,with maximum in control group(Day 3-35,Day 9-46.98) and minimum in Chloroquine arm(Day 3-14.06.Day 9-19.92).The percentage of parasitemia was compared using Mann-Whitney U test depicting that all test groups exhibited reduction in parasitemia as compared to control(P-value【0.002 for all groups).These groups showed similar percentage of survival as Chloroquine.Conclusions:The present investigation demonstrated the anti-plasmodial effects of H.antidysentrica and A.indica.which are two most commonly used medicinal plants in Ayurved for treatment of fever.

Protective Roles of Shilajit in Modulating Resistin,Adiponectin,and Cytokines in Rats with Non-alcoholic Fatty Liver Disease

Objective:To evaluate the effect of Shilajit,a medicine of Ayurveda,on the serum changes in cytokines and adipokines caused by non-alcoholic fatty liver disease(NAFLD).Methods:After establishing fatty liver models by feeding a high-fat diet(HFD)for 12 weeks,35 Wistar male rats were randomly divided into5 groups,including control(standard diet),Veh(HFD+vehicle),high-dose Shilajit[H-Sh,HFD+250 mg/(kg·d)Shilajit],low-dose Shilajit[L-Sh,HFD+150 mg/(kg·d)Shilajit],and pioglitazone[HFD+10 mg/(kg·d)pioglitazone]groups,7 rats in each group.After 2-week of gavage administration,serum levels of glucose,insulin,interleukin1 beta(IL-1β),IL-6,IL-10,tumor necrosis factor-alpha(TNF-α),adiponectin,and resistin were measured,and insulin resistance index(HOMA-IR)was calculated.Results:After NAFLD induction,the serum level of IL-10 significantly increased and serum IL-1β,TNF-αlevels significantly decreased by injection of both doses of Shilajit and pioglitazone(P<0.05).Increases in serum glucose level and homeostasis model of HOMA-IR were reduced by L-Sh and H-Sh treatment in NAFLD rats(P<0.05).Both doses of Shilajit increased adiponectin and decreased serum resistin levels(P<0.05).Conclusion:The probable protective role of Shilajit in NAFLD model rats may be via modulating the serum levels of IL-1β,TNF-α,IL-10,adipokine and resistin,and reducing of HOMA-IR.

Effect of Chlorophytum Borivilianum Santapau and Fernandes on Sexual Dysfunction in Hyperglycemic Male Rats

Objective:To investigate the effects of Chlorophytum borivilianum(CB) on sexual dysfunction, loss of body weight,and lack of libido in hyperglycemic rats induced with streptozotocin or alloxan.Methods: Wistar strain male albino rats were divided into five groups of six animals each:the control group(2% polyvinylpyrollidone solution),the streptozotocin control group(50 mg/kg),the alloxan control group(100 mg/kg), the streptozotocin + CB treated group(200 mg/kg),and the alloxan + CB treated group(200 mg/kg).O...

Awareness,practice and views about integrating AYUSH in allopathic curriculum of allopathic doctors and interns in a tertiary care teaching hospital in New Delhi,India

Objective： To assess the knowledge, attitude, perception and practice of Ayurveda, yoga, Unani, Siddha, homeopathy and naturopathy （AYUSH） among allopathic doctors and interns and determine their opin- ion regarding integration of AYUSH education within the allopathic curriculum. Methods： This prospective, cross sectional study was conducted in a tertiary care teaching Hospital, New Delhi, India, from March 2016 to March 2017. A survey of 500 aUopathic doctors and 150 interns was performed using a structured questionnaire. Results： A majority of doctors （95.2%） were aware of the term AYUSH and had knowledge of yoga （70.6%）, homeopathy （55.6%）, Ayurveda （50.3%）, Siddha （47.8%）, naturopathy （32.9%） and Unani （28.9%）. Most of the participants （63.0%） felt that therapies under AYUSH are effective. A majority （84.0%） of the doctors were of the view that more research is required in the field of AYUSH. While homeopathy （44.0%） was the most common system used by doctors for themselves, yoga was the therapy most commonly （60.0%） recommended to patients. Nearly half of the doctors （46.7%） recommended AYUSH to their patients, mainly for chronic illness （74.0%）. A majority （77.5%） of the respondents agreed that students of allopathic med- icine should be familiarized with AYUSH. The modes of incorporation of AYUSH into the medical curriculum most commonly suggested by respondents were optional courses （54.5%） and introductory lectures （42.3%）. Conclusion： Doctors and interns ofallopathic medicine are aware of AYUSH systems. They use it for them- selves and recommend it to patients. They believe that familiarization of Bachelor of Medicine and Bachelor of Surgery students with AYUSH therapies and their integration with allopathic medicine may help in improving patient care.

Microwave Assisted Extraction,Antioxidant Potential and Chromatographic Studies of Some Rasayana Drugs

Objective： To study and compare the conventional extraction procedure with microwave assisted extraction （MAE） for some Ayurvedic Rasayana drugs and to evaluate their antioxidant potential and carry out the characterization of extracts by thin layer chromatography. Methods： Three Ayurvedic rasayana plants Allium sativum Linn., Bombax ceiba Linn. and Inula racemosa Hook. were evaluated for an improved MAE methodology by determining the effects of grinding degree, extraction solvent, effect of dielectric constant and duration of time on the extractive value. Antioxidant potential of all three drugs was evaluated with 2,2-diphenyl-l-picrylhydrazyl （DPPH） radical scavenging activity and reducing power was determined by using Gallic acid as standard. Further thin layer chromatographic （TLC） analysis was performed on pre-activated Silica Gel G plates and Rf value were compared with those reported for the important biomarkers. Results： The total extractive value for Allium sativum Linn. was 36.95% （w/w） and 49.95% （w/w） for ethanol extraction respectively. In case of Bombax ceiba Linn. the yield of aqueous extract by MAE was 50% （w/w） compared to 42% （w/w） in ethanol （50% v/v）. Percent yield of Inula racernosa Hook. in aqueous extract was found to be 27.55% （w/w） which was better than ethanol extract （50%） where the yield was 25.95% （w/w）. Upon antioxidant activity evaluation A. safivum extract showed an absorbance of 0.980 ± 0.92 at concentration of 500 μg with maximum reducing capacity. This was followed by B. ceiba Linn. 0.825 ± 0.98 and I. racemosa Hook. with 0.799 ± 2.01 at a concentration of 500 μ g. TLC based standardization of A. sativum Linn. extract shows single spot with Rf value of 0.38, B. ceiba Linn. extract shows Rf values were 0.23, 0.58, 0.77, 0.92 and I. racemosa Hook. extract spot had a Rf value of 0.72. Conclusions： A significant improvement in extractive values was observed as a factor of time and other advantages by using MAE technology. All three drugs have high antioxidant potential and a TLC profiling similar to reported ones. The presence of fructan type polysaccharide can be further utilized for bioactivity directed fracUonation and evaluation of immunomodulatory activity.

Curcumin – A review on multipotential phytocompound

Curcumin, a polyphenol (diferuloylmethane), is a derivative obtained from the Curcuma longa. It has many beneficial functions, including pain-killing, activity against reactive oxygen species, preventing inflammation and antibacterial activities, for which it has been used for centuries in Ayurvedic medication. The mechanisms showing curcumin activity involve a grouping of signaling pathways in the cell at multiple stages. Recently, the anticancer effects of curcumin were studied on different pathways, including the gene expression for cancer, its spread, the regulation of cell cycle, programmed cell death, and tumor expression. All these studies suggest enormous potential of curcumin in cancer therapy. It has many more potential benefits against cardiovascular diseases, reactive oxygen species, bacteria and fungi. The present review provides a brief description of the studies conducted and the information supportive to pharmaceutical activities of curcumin. It also considers anticancer applications and clinical benefits of nano-formulations of curcumin.