Clinical evaluation of the hepatoprotective effect of Katuki (Picrorhiza kurroa Royle ex Benth.) processed in Guduchi (Tinospora cordifolia Wild.) Miers in patients receiving lipid lowering drugs (Statins)
Abstract
The hypolipidaemic drugs have attracted considerable attention because of their potential to prevent cardiovascular disease by retarding the accelerated atherosclerosis in hyperlipidaemic individuals. Statins are the first choice drugs for primary hyperlipidaemias with raised LDL and total cholesterol levels, with or without raised triglycerides levels, as well as for secondary hypercholesterolemia. Statin therapy is commonly associated with liver damage in terms of elevated aminotransaminases. Simultaneous use of hepatotoxicity reducing formulation is desirable for successful continuation of HMG-CoA reductase inhibitor (stains) over a desired period in hyperlipidaemic patients. So, the present clinical study was planned to evaluate the hepatoprotective effect of Katuki (Picrorhiza karma Royle ex Benth.) processed in Guduchi [Tinospora cordifolia (Wild.) Miers], on scientific parameters. In the present clinical trial, two groups of patients receiving standardized lipid lowering drug (Atrorvastatin 20 mg, twice daily) have been studied to evaluate the hepatoprotective effect of these drugs. The first group was given 2 gm of Katuki processed in Guduchi, twice daily with statin therapy. The second group was given 500 mg of starch powder filled in capsules, twice daily with statin therapy. The trial was conducted for three months and liver functions test were periodically evaluated to assess the hepatoprotective effect of drugs under trial. At the end of the trial, trial group exhibited its hepatoprotective efficiency over the control.
... T. cordifolia, well reported for its hepatoprotective activity is known to prevent dyslipidemia and reduce serum AST, ALT, and ALP (Alkaline phosphatase) levels as reported in several pre-clinical studies [15,16]. A clinical trial on hyperlipidemia patients who were on standard statin therapy was conducted using katuki (Picrorhiza kurroa) processed in T. cordifolia [17]. Serum levels of AST, ALT, and ALP were observed to improve significantly in the drug trial group patients as compared to the control group (placebo), thus suggesting the hepatoprotective potential of the plant extract. ...
Background
Sleep deprivation (SD) due to an unhealthy lifestyle poses an oxidative challenge and is closely associated with an increased risk and prevalence of different metabolic disorders. Although the negative consequences of SD are well reported on mental health little is known about its detrimental effects on liver function and lipid metabolism. Tinospora cordifolia is reported for its hepatoprotective activity in different pre-clinical model systems. The current study was designed to elucidate the cumulative effects of aging and acute SD on liver functions, oxidative stress, and lipid metabolism, and their management by butanol extract of T. cordifolia (B-TCE) using middle-aged female acyclic rats as the model system.
Results
Rats were divided into 4 groups: (1) Vehicle-undisturbed (VUD) (2) Vehicle-sleep deprived (VSD) (3) B-TCE pre-treated sleep-deprived (TSD) (4) B-TCE pre-treated undisturbed sleep (TUD). TSD and TUD groups were given 35 mg/kg of B-TCE once daily for 15 days followed by 12 h of sleep deprivation (6 a.m.–6 p.m.) of VSD and TSD group animals using the gentle-handling method while VUD and TUD group animals were left undisturbed. SD of VSD group animals increased oxidative stress, liver function disruption, and dyslipidemia which were ameliorated by B-TCE pre-treatment. Further, B-TCE was observed to target AMPK and its downstream lipid metabolism pathways as well as the p-Akt/cyclinD1/p-bad pathway of cell survival as possible underlying mechanisms of its hepatoprotective activity.
Conclusions
These findings suggest that B-TCE being a multi-component extract may be a potential agent in curtailing sleep-related problems and preventing SD-associated hepatotoxicity and dyslipidemia in postmenopausal women.
Graphical abstract
Graphical abstract to depict mechanism of action of B-TCE on liver function and lipid metabolism.
... Benth (Family Scrophularaceae) commonly called Kutki or Kutka is a recognized herb in the Ayurvedic and Chinese system of traditional medicine. It is a wonder herb with hepatoprotective, [1][2][3][4] anticholestatic, [5] antioxidant, [6] antidiabetic, [7] and immune-modulating properties. [8][9][10] The leaves, root and rhizome of Picrorhiza are used to treat liver and upper respiratory tract disorders, chronic diarrhea, and scorpion sting. ...
... A clinical trial to evaluate the hepatoprotective activity of Kutki concluded that patients who received 2 g of Kutki processed in Guduchi along with statin therapy showed hepatoprotective effect over the control group [59]. ...
Picrorhiza kurroa Royle ex Benth. (Family: Plantaginaceae) is a well-recognized an Ayurvedic herb. It is commonly called “Kutki” or “Kurro” and ‘Indian gentian’. Iridoid glycosides are the plant’s bioactive constituents and accountable for the bitter taste and medicinal properties of the plant. The iridoid glycosides such as picrosides and other active metabolites of the plant exhibited many pharmacological activities like hepatoprotective, antioxidant, anti-inflammatory, anticancer, immunomodulator, anti-ulcerative colitis, antimicrobial etc. This review aims to provide updated information on the ethnobotany, synthetic phytochemistry, pharmacological potential, safety and toxicology of P. kurroa and its active metabolites. Indiscriminate exploitation, ecological destruction of natural habitats, slower plant growth and unawareness regarding cultivation and uprooting of plants has brought kutki as an endangered status. So, various techniques used for the conservation and production of bioactive metabolites from P. kurroa have also been reported. Information on the plant has been collected from Science Direct, Google Scholar, PubMed, Scopus by using ‘Picrorhiza kurroa’, ‘Picroside-‘, ‘Picroside-II’, ‘Picroliv’, ‘Immunomodulator’ keywords. All studies on ethnobotany, phytochemistry and pharmacology of plant from 2010- 2020 were comprised in this review article. The possible directions for the future research have also been outlined in brief in review article.
... P. kurroa has been shown to have hepatoprotective activity but evidence is limited by the lack of its clinical studies. Despite the multitude of animal research on this topic, there appear to be only three studies in humans which showed that low doses of kutkin were effective against viral hepatitis (Keche et al., 2010;Singh and Sharma, 2011;Vaidya et al., 1996). ...
Picrorhiza kurroa Royle ex Benth is one of the most important medicinal plants, commonly used in traditional medicinal systems. The plant has several medicinal properties due to the presence of bio active components viz., Picroside I and Picroside II, cucurbitacins and phenolic components. These chemical compounds are found in the roots and rhizomes of this herb, and are used to cure various ailments such as liver problems, spleen disorder, fever and asthma. World annual demand of P. kurroa is 500 tons per year while production is 375 tons (Thani et al., 2018). It has become endangered in various regions due to indiscriminate exploitation for medicinal purposes. Immediate steps need to be taken for the conservation of this medicinal herb otherwise it will lead to extinction. This paper gives an overview of geographic distribution, taxonomic feature, agrotechnology, phyto-chemistry, molecular studies, and conservation of P. kurroa.
... It is a well-recognized herb in the Ayurvedic and Chinese traditional medicine. It is a wonder herb with hepatoprotective (1)(2)(3)(4), anticholestatic (5), antioxidant (6), antidiabetic (7) and immune-modulating properties (8)(9)(10). The leaves, root and rhizome of Picrorhiza are effective in numerous ailments namely liver and upper respiratory tract illnesses, chronic diarrhea, malaria, jaundice, epilepsy, paralysis, rheumatoid arthritis and skin diseases (11)(12)(13)(14). ...
Introduction: The Picrorhiza kurroa rhizome has a long history of use in Indian Ayurvedic and Chinese system of medicine for the treatment of a wide spectrum of diseases. Today it is viewed as an important therapeutic target in both Western and Eastern medicinal systems. This work was aimed to study the clastogenic effect of Picrorhiza kurroa rhizome extract on cultured human peripheral blood lymphocytes. Methods: Hydroalcoholic extract of rhizome was prepared and mammalian chromosomal aberration test was conducted using cultured human peripheral blood lymphocytes. The study was performed in two independent phases where the human peripheral blood lymphocytes were exposed to various of the extract in absence and presence of metabolic activation system for a continuous and short duration. Results: Picrorhiza kurroa rhizome extract did not induce chromosome aberration up to 2500 μg/mL in final culture concentration in the presence (1% v/v) and absence of metabolic activation. Conclusion: Picrorhiza kurroa rhizome extract is completely safe to be used as a medicine since it manifest its healing effects without causing genotoxicity.
The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.
Traditional remedies for the treatment of various ailments are gaining popularity. Traditionally, one of the most valuable therapeutic herbs has been Picrorhiza kurroa Royle ex Benth. Traditional and folk uses of P. kurroa include chronic constipation, skin-related problems, burning sensation, chronic reoccurring fever, jaundice, heart problems, breathing, digestion, allergy, tuberculosis, blood-related problems, prediabetes and obesity, laxative, cholagogue, and liver stimulatory. Phytoconstituents such as glycosides, alkaloids, cucurbitacins, iridoids, phenolics, and terpenes in P. kurroa have shown promising pharmacological potential. In order to uncover novel compounds that may cure chronic illnesses, such as cardiovascular, diabetes, cancer, respiratory, and hepatoprotective diseases, the screening of P. kurroa is essential. This study comprehensively evaluated the ethnopharmacological efficacy, phytochemistry, pharmacological activity, dose, and toxicity of P. kurroa. This review provides comprehensive insights into this traditional medication for future research and therapeutic application. The purpose of this review article was to determine the pharmacological effects of P. kurroa on a variety of disorders. P. kurroa may be a natural alternative to the standard treatment for eradicating newly evolving diseases. This study is intended as a resource for future fundamental and clinical investigations.
Picrorhiza kurroa Royle ex Benth, Kutki (P.kurroa) is an important medicinal plant, traditionally recommended and used in Ayurveda for millennia, with certain cautions. There has been a significant revival of keen interest in its pharmacology, pharmacognosy, and phytochemistry for the last few decades. The evidence of its hepatoprotective activity, in experimental and clinical studies, accelerated the correlation of the specific phytochemical constituents of P.kurroa with precise pharmacological activities. Iridoid glycosides, particularly picrosides, emerged as the active molecules. For effective translation of traditional remedies into modern therapy, value addition by mechanistic understanding of molecular actions, drug targets, the degrees of efficacy and safety as well as convenient dosage forms is needed. Reverse pharmacology approach and phytopharmaceutical drug category facilitate such a translation. The present review illustrates how a potential translation of traditional practices of using P.kurroa into a phytochemically standardized, clinically targeted natural product for global unmet medical needs viz. Fatty liver disease can be attained.
Liver is known as a vital organ and play a crucial role in the metabolism and it is causes it to succumb to numerous hepatic diseases. Synthetic drugs exploited in the treatment of liver diseases are incompetent and may sometimes lead to serious side-effects. In this context, herbal therapy has emerged as a proficient approach with good values in treating hepatic diseases. Medicinal plants may serve as a vital source of potentially useful new compounds for the development of effective therapy to combat a variety of liver problems. Many herbs have been proven to be effectual as hepato protective agents while many more are claimed to be hepato protective but lack any such scientific evidence to support such claims. Developing a satisfactory herbal therapy to treat severe liver diseases requires systematic investigation of properties such as antiviral action (Hepatitis B, Hepatitis C), anti-hepatotoxicity (antioxidants), stimulation of liver regeneration and choleretic activity. Formulation of herbal medicines with standards of safety and efficacy can revitalize treatment of liver disorders. In the present study, the efficacy of polyherbal herbal formulation Hepashrey Syrup has been studied in human with history of liver disorders twice daily dosage for a period of one month at OPD of JSS Ayurveda Medical College, Mysore. The initial results are reported with encouraging results on liver. We conclude that Hepashrey syrup possess hepato protective effect in patients. This protective effect of Hepashrey syrup can be attributed to the anti-inflammatory, anti-oxidative, and hepato protective properties of the component herbs.
Diabetes becomes a global health burden, affecting almost one third of world population. This figure is self explanatory for its alarming growth and concern to be given for its prevention and management. It is erroneous to treat it as a disease rather it should be treated as a syndrome, because rarely it is presented in its discrete form i.e. only hyperglycemia as a clinical feature. Being a metabolic disease it is almost always accompanied with many other diseases like hypothyroidism, hypertension, fatty liver disease, obesity, dyslipidemia, etc. According to the known pathophysiology of diabetes, hyperglycemia is said to be responsible for dyslipidemia, constant high sugar level in blood produces dreaded effect at micro as well as macro- vascular level. This established pathology of the disease revolves around high glucose level in blood and make it the diagnostic parameter for diabetes. Although the cause of hyperglycemia are also well defined but there is one missing link which is totally neglected by the modern science i.e., role of liver in the pathogenesis of diabetes. Do any way hampered liver functions affect insulin production or its utilization by the cell- the question that required answer. This clinical trial is based on materializing the concept that effective bile secretion improves insulin activity. This is a pilot study carried out on 15 known patient of non insulin dependent diabetes. The study showed that 66.6% patient has diabetes associated with hypothyroidism followed by dyslipidemia (60%). The study drug shows significant (p< 0.001) reduction in both FBS and PPBS and improve the presenting symptoms effectively.
Hepatitis infection has become a major worldwide health problem because the potential nature of course of the disease to cirrhosis and the hepatocellular carcinoma (HCC). Acute viral infection is the most common cause of all forms of hepatitis. The viral hepatitis have been thought to be self limiting in nature but sometimes majority of patients of viral hepatitis have been observed ending up with a serious complications like hepatic failure, etc. So, the clinical study was planned to evaluate the hepatoprotective effect of Bhyumyamalki (Phyllanthus fraternus Webster) and Phaltrikadi decoction (an Ayurvedic herbal composition) on scientific parameters. In the clinical trial, three groups of patients of viral hepatitis have been studied to evaluate the hepatoprotective effect of Bhumyamalki and Phaltrikadi decoction. The first group was given 50 ml of freshly prepared Bhumyamalki decoction, made from 10 gm of crude drug, twice daily. The second group was given a standardized decoction of herbal composition Phaltrikadi decoction, in a dosage of 50 ml made from 10 gm of crude drug, twice daily. The third group was given 100 gm of glucose powder daily. The trial was conducted for one month and liver functions test were periodically evaluated to assess the hepatoprotective effect of drugs under trial. At the end of the trial, group first and second exhibited hepatoprotective efficiency over the control.
The alcoholic extract of the roots of T. cordifolia was investigated for its effect on brain amine levels in stressed rats. It was found to possess normalising activity against stress induced changes in norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIA) levels.
The ethanol extracts of the roots of T. cordifolia Miers and C. asiatica Linn were observed to induce a marked protective action against an 8 h restraint stress induced ulcerization, the activity being comparable to that of diazepam.
Powdered roots of Picrorhiza kurrooa (PK), its alcoholic extract (AEPK) and active constituents kutkin, picroside-1 and kutkoside demonstrated antiinflammatory activity (AIA) in a variety of test models. Significant AIA was recorded in adjuvant-induced and formaldehyde arthritis in rats and mice. In carrageenan-induced oedema inhibitory activity was remarkably enhanced upon intraperitoneal treatment in rats and mice. Kutkin exhibited significant action in dextran-induced oedema in rats. It inhibited acetic acid induced vascular permeability in mice and leucocyte migration in rats. Kutkin lacked any analgesic, antipyretic or ulcerogenic effect.
Extract of Tinospora cordifolia has been shown to inhibit the lipid peroxidation and superoxide and hydroxyl radicals in vitro. Concentration needed for 50% inhibition was 6 mg and 12.5 mg/ml, respectively. The extract was also found to reduce the toxic side effects of cyclophosphamide administration (25 mg/kg b.wt, 10 days) in mice hematological system by the free radical formation as seen from total white blood cell count, bone marrow cellularity and alpha-esterase positive cells. Moreover, administration of the extract partially reduced the elevated lipid peroxides in serum and liver as well as alkaline phosphatase and glutamine pyruvate transaminase. This indicates the use of Tinospora extract in reducing the chemotoxicity induced by free radical forming chemicals.
Picroliv, the active principle of Picrorhiza kurrooa, and its main components which are a mixture of the iridoid glycosides, picroside-I and kutkoside, were studied in vitro as potential scavengers of oxygen free radicals. The superoxide (O2-) anions generated in a xanthine-xanthine oxidase system, as measured in terms of uric acid formed and the reduction of nitroblue tetrazolium were shown to be suppressed by picroliv, picroside-I and kutkoside. Picroliv as well as both glycosides inhibited the non-enzymic generation of O2- anions in a phenazine methosulphate NADH system. Malonaldehyde (MDA) generation in rat liver microsomes as stimulated by both the ascorbate-Fe2+ and NADPH-ADP-Fe2+ systems was shown to be inhibited by the Picroliv glycosides. Known antioxidants tocopherol (vitamin E) and butylated hydroxyanisole (BHA) were also compared with regard to their antioxidant actions in the above system. It was found that BHA afforded protection against ascorbate-Fe(2+)-induced MDA formation in microsomes but did not interfere with enzymic or non-enzymic O2- anion generation; and tocopherol inhibited lipid peroxidation in microsomes by both prooxidant systems and the generation of O2- anions in the non-enzymic system but did not interfere with xanthine oxidase activity. The present study shows that picroliv, picroside-I and kutkoside possess the properties of antioxidants which appear to be mediated through activity like that of superoxide dismutase, metal ion chelators and xanthine oxidase inhibitors.
Picroliv, the hepatoprotective principle of the plant Picrorhiza kurroa, showed a dose-dependent (1.5-12 mg/kg x 7) choleretic effect in conscious rats and anaesthetised guinea pigs. It also possessed a marked anticholestatic effect against paracetamol- and ethynylestradiol-induced cholestasis. It antagonised the changes in bile volume as well as the contents (bile salts and bile acids). Silymarin, a known hepatoprotective agent, was tested simultaneously for comparison. Picroliv was found to be a more potent choleretic and anticholestatic agent than silymarin.
A clinical study was undertaken to determine the immune status of patients with obstructive jaundice. Screening of 16 patients for phagocytic and microbicidal activity of polymorphonuclear cells (PMN) revealed a significant depression (21.2 +/- 3.7% phagocytosis and 20.85 +/- 4.5% intracellular killing) of these functions, as compared to normal values (30.37 +/- 5.1% and 26.41 +/- 4.3% respectively). An animal model of cholestasis was also established, using rats, in which a significant depression of activity of PMN and peritoneal macrophages was observed. These cellular abnormalities were found to precede and predispose to infection. The rats also showed an increased susceptibility to Escherichia coli infection (mortality rate 77.78%). A defect was detected in their serum responsible for depressing the function of phagocytic cells. An attempt was made to improve this immunosuppression by treating the rats with water extract of T. cordifolia 100 mg/kg for 7 days, following development of cholestasis. The extract improved the cellular immune functions. Mortality rate following Esch. coli infection was significantly reduced to 16.67 per cent. This study showed that cholestasis results in immunosuppression and therefore indicates the need for an immunomodulator in management of obstructive jaundice. The plant T. cordifolia seems to meet this need by consolidating host defence mechanism.