What is Picrorrhiza Root and it's major application?

  seminal trace...Picrorrhiza Root.Picrorrhiza kurroa.10:1Extract.Hu Huang Lian,Picrorhiza kurrooa Royle ex Benth. or Picrorhiza scrophulariaeflora Pennell,Picrorrhiza kurroa,Hu Huang Lian.Hu Lian.Kutki; Katuka; Hellbore,Katuki, Kurri, Katuko, Kuru, Katukarogani.picroliv, Picrorhiza kurroa, Picrorhiza kurroa extract, Picrorhiza kurroa Royle, Picrorhiza kurroa Royle ex Benth., Picrorhiza lindleyana Steud., Picrorrhiza kurroa.Black hellebore,Kutkin,picrosides I,picrosides II,picrosides III,Picroside IV,kutkoside,cucurbitacin glycosides,highly oxygenated triterpenes,,apocycynin,androsin,,Acute Hepatitis and Chronic Hepatitis,.Allergies,Anti-Inflammatory,Asthma,Hypoxia,Immune Enhancing,Increases Cellular Oxygenation,Vitiligo......

 

 Basic Botanical Info of Picrorrhiza kurroa:
 Phytochemical and Constituents of Picrorrhiza Root:
 Indications of Picrorrhiza Root:
 Western Properties and Reported Uses:
 Action and Classical Note of Picrorrhiza Root:
 Picrorrhiza Root:Pharmacology
 Dosage,Administrations and Safety:
 Application Case Study:Liver function improvement formulation
 Research Update:Picrorrhiza kurroa and Picrorhiza scrophulariaeflora


   Basic Botanical Info of Picrorrhiza kurroa:

 Picrorrhiza Root
 Botanical Name:Picrorrhiza kurroa
 Botanical Source:Picrorrhiza kurroa Royle ex Benth. or Picrorhiza scrophulariaeflora Pennell.
 Family: Scrofulariaceae
 Pinyin Name:Hu Huang Lian
 English:Figwortflower Picrorhiza Rhizome
 Synoms:Picrorrhiza kurroa,Hu Huang Lian.Hu Lian.Kutki; Katuka; Hellbore,Katuki, Kurri, Katuko, Kuru, Katukarogani.picroliv, Picrorhiza kurroa, Picrorhiza kurroa extract, Picrorhiza kurroa Royle, Picrorhiza kurroa Royle ex Benth., Picrorhiza lindleyana Steud., Picrorrhiza kurroa.Black hellebore.
 Medicinal Parts Used:Dried Root (exceptionally bitter)
 Origin: A small herb which grows in the Himalayas at 3000-5000m.

  Picrorrhiza Root Brief:
 
 Picrorrhiza is a small perennial herb from the Scrophulariaceae family.Picrorhiza kurroa has a long, creeping rootstock that is bitter in taste, and grows in rock crevices and moist, sandy soil. The leaves of the plant are flat, oval, and sharply serrated. The flowers, which appear June through August, are white or pale purple and borne on a tall spike; manual harvesting of the plant takes place October through December.The plant is self-regenerating but unregulated over-harvesting has caused it to be threatened to near extinction.

 Habitat: The plant is naturally distributed in alpine and temperate regions of Himalaya from 2500 to 3500 m. It is a perennial creeping herb, which spreads by stolons. A whorl of radical leaves arise from rhizome tip. The flowering scape attains an average height of 16.0 to 17.5 cm.Majorly output from Tibetan towns of China,such as Nie La Mu,Ya Dong,Cuo Na,Bo Mi,etc.and West north regions of Yunnan Province,west of SiChuan province of China.other origins including Nepal,Sikkim,Bhutan and India.

 Root morphology: Adventitious roots arise from the rhizome. Maximum average root length (38 cm) was observed in case of PK-6. Maximum average primary roots were recorded for PK6 and PK7. PK5 recorded highest number of secondary roots and maximum fresh weight (230 g) of the roots.

 Flowering: Flowering occurs in one or two phases depending upon altitude of the growing site. Under relatively lower elevation of 2500-3500 m msl, the fist phase starts in 1st week of May and continues up to 3rd week of June and the second flowering begins in August and continues up to end of September. In alpine regions (>4000 m), flowering occurs only once in July-August and seeds develop in September. Flowers are borne on a scape in an indeterminate spike forming more or less a triangular head. Flowers are purple coloured, bisexual and having convex thalamus.

 Fruit: Fruit is an ovoid capsule which dehisces by means of lateral splits. The average dimension of fruits was 9 x 5 mm.
 Seed: The extremely small sized seed is 1.3 x 1 mm in size. Embryo is enclosed in the large bladdery loose hyaline reticulate testa. The seeds test weight was about 57.5 mg.

 Ethno-botanical information:Nomadic commodities from Himalaya keep this drug at their place for use as home remedy for various stomach disorders. In Nepal root paste is applied for speedy healing of wounds. The decoction of roots in water is given with salt to febrile cattle as antipyretic.

 

   Phytochemical and Constituents of Picrorrhiza Root:

 Dry root Rhizome contains Kutkin 3.4% and D-Mannitol 0.5%,Vanillic acid 0.1%,Kutkiol,Kutkistero1,0.18% and Apocynin.Hu Huang Lian Toxin is the stable mix crystal of Picroside I and Kutkoside.Picroside II.Iridoid glycosides such as picrosides(picrosides I,picrosides II,picrosides III),kutkoside,cucurbitacin glycosides (highly oxygenated triterpenes),apocycynin,androsin.

 Kutkin, a bitter glycosidal principle, is reported. Also isolated D-mannitol, vanillic acid and some steroids are present. Kutkin was later shown to be a stable mixed crystal of two C-9 iridoid glycosides-Picroside I and Kutakosid. Apocynin has been isolated from the plant. Picroside II has been isolated and shown to have hepatoprotective activity. With the help of preparative HPLC, larger Quantities of picrosides have been isolated, permitting precise structure identification and biological experiments.

 Kutkin is the active principal of Picrorhiza kurroa and is comprised of kutkoside and the iridoid glycoside picrosides I, II, and III. Other identified active constituents are apocynin, drosin, and nine cucurbitacin glycosidesApocynin is a catechol that has been shown to inhibit neutrophil oxidative burst in addition to being a powerful anti-inflammatory agent, while the curcubitacins have been shown to be highly cytotoxic and possess antitumor effects.

 D-Mannitol, or 1,2,3,4,5,6-hexanehexol (C6H8(OH)6, is a polyol (an alcohol and a sugar). D-Mannitol is similar to xylitol and sorbitol except it tends to lose a hydrogen molecule in aqueous mixtures and become acidic. Mannitol is often used as a sweetner or laxative.

 Latest research findings following three compounds were isolated from the whole plant:

 1.25-Acetoxy-2beta-Glucosyloxy-3,16,20-Trihydroxy-9-Methyl-18-Norlanost-5,23-Dien-22-One
 2.2-Beta-Glucosyloxy-16,20,22-Trihydroxy-9-Methyl-19-Norlanosta-5,24-Diene-3,11-Dione
 3.2-Beta-Glucosyloxy-3,16,20,25-Tetrahydroxy-9-Methyl-19-Norlanosta-5,23-Diene-11,22-Dione
 

 Where as ARVENIN-III has been isolated from roots and rest of the followings namely Apocynin, D-Mannitol,Glucose,Glucosido-Vanilloyl-Glucose, Kurrin, Kuthinol, Kuthirterol,Kutkin,Kutkiol,Kutkisterol, Kutkoside, Picrorhizin, Picroside-I,Picroside-II,Tripalmitin and Vanillic-Acid are isolated from rhizome.

 Extensive work on the chemistry of P.kurroa has been initiated at RRL Jammu. Following six compounds have been earmarked as marker compounds. Structures of Picroside I, Picroside II, Picroside IV, Apocynin, Androcynin and PK-3 as showing on picture accordingly.

 Fruit contains Vitamin C,glicosides,starch and protein.

 

   Indications of Picrorrhiza Root:

 Dysentery or jaundice caused by damp-heat; hemorrhoids; consumptive fever and fever in infantile malnutrition due to digestive disturbance.
 -drain damp heat,dysentery,sores.
 -clear deficient heat,yin deficiency heat symptoms.
 -clear heat¨Creduce childhood nutritional impairment,abdominal distention,afternoon fever,dysent.

 dried rhizome is antibacterial, anti-inflammatory, antiperiodic, cathartic (in large doses), cholagogue, laxative (in smaller doses), stomachic and bitter tonic.Current research on Picrorhiza kurroa has focused on its hepatoprotective, anticholestatic, antioxidant, and immune-modulating activity.The rhizome of Picrorhiza has been traditionally used to treat worms, constipation, low fever, scorpion sting, asthma and ailments affecting the liver. Current research on Picrorhiza kurroa has focused on its hepatoprotective, anticholestatic, antioxidant, and immune-modulating activity.

 The root contains a number of very bitter glucosides including kutkin and picrorhizin. It also contains apocynin, which is powerfully anti-inflammatory and reduces platelet aggregation.


   Western Properties and Reported Uses:

 Anti-bacterial,anti-fungal,anti-pyretic,cholagogue,stomachic,immune stimulant,anti-inflammatory,anti-coagulant,anti-parastatic(active against Leishmaniasis)

 Notes Used for insufficient stomach acid secretion,indigestion,jaudice,hepatitis,cirrhosis,constipation,diarrhea,dysentery,malaria,conjunctivitis,hemorrhoids,infantile seizures,immune system tonification,intestinal parasites,bladder infections,viral infections,yeast infections

 Frequently Reported Uses:Antioxidant,Hepatitis (Acute, Chronic), Hepatoprotective,Hepatoprotective Against Psychotropics And Other Pharmaceuticals.
 Other Reported Uses:Allergies,Anti-Inflammatory,Asthma,Hypoxia,Immune Enhancing,Increases Cellular Oxygenation,Vitiligo

 

   Action and Classical Note of Picrorrhiza Root:

 Acute and chronic infections.
 Anti-allergic,helps with allergies.
 Anti-inflammatory,an agent to ease inflammation.
 Bitter tonic,applied to bitter tasting drugs which act on the mucous membranes of the mouth and stomach to increase appetite and promote digestion]
 Hepatoprotective,protects the liver.
 Immunostimulant,Immune System Conditions,weakened immunity.
 Treatment for allergies.
 Treatment for autoimmune disorders.
 Liver Conditions,liver infections,toxic liver damage.
 Respiratory Tract Conditions
 Immune System Conditions:acute and chronic infections,treatment for allergies,treatment for autoimmune disorders,weakened immunity.

 Remedies For:Protects the liver against hepatotoxins, hepatoprotective properties, Potent antioxidant activity, Modulates liver enzyme levels, anti-inflammatory action anti-allergy action.

  Classical Note:

 First registered in Xin Xiu Ben Cao
 Yao Pin Hua Yinoted: "Hu Hunag Lian,enter blood seperately and clear heat.Dan Xi Said:Bone heat and pain for hot accumulations,this herb could be used to cool the blood and benefit Yin and it functions fascinating even if singely used,for case like hot night and calm in day,its hot in blood,combine Hu Huang Lian with Chuan Xiong and Dang Gui for soup decoction,twice daily,heat get rid of quickly and effectively.¡±
 Ben Cao Zheng Jingnoted: "For cases fever,heat,diarrhea,rectocele,tache and sore,gonorrheasyphilis and other cases,caused by yin fire accumulation,only Hu Huang Lian could cure."

 

   Picrorrhiza Root:Pharmacology

 Alcohloic extract of the plant and kutkin possess hepatoprotective activity. Plant is a potent immunostimulant of both cell mediated and humoral immunity and exhibits choleretic activity in dogs. Picrorhiza kurroa is also benefical in the management of bronchial asthma.

  Mechanisms of Action:

 The hepatoprotective action of Picrorhiza kurroa is not fully understood but may be attributed to Picrorhiza's ability to inhibit the generation of oxygen anions and to scavenge free radicals.Picrorhiza's antioxidant effect has been shown to be similar to that of superoxide dismutase, metal-ion chelators, and xanthine oxidase inhibitors.In rats infected, with malaria, Picrorhiza restored depleted glutathione levels, thereby enhancing detoxification and antioxidation, and helping maintain a normal oxidation-reduction balance.In this same animal model, Picrorhiza also demonstrated an anti-lipid peroxidative effect.Like silymarin, Picrorhiza has been shown to stimulate liver regeneration in rats, possibly via stimulation of nucleic acid and protein synthesis. Picrorhiza's anti-inflammatory action is attributed to the apocynin constituent, which has been shown to have potent anti-inflammatory properties in addition to inhibiting oxidative burst in neutrophils.Although the mechanism is unclear, animal studies indicate Picrorhiza's constituents exhibit a strong anticholestatic activity against a variety of liver-toxic substances, appearing to be even more potent than silymarin. Picrorhiza also exhibits a dose-dependent choleretic activity, evidenced by an increase in bile salts and acids, and bile flow.
 

  Asthma/Allergy:

 Antiasthamatic Activity:P.kurroa has been studied extensively for its anti asthmatic activity. The crude extract of P.kurroa roots reduced the frequency and severity of asthmatic attacks and the need for regular bronchodilators. The activity has been attributed to compounds such as androsin and apocynin, which have been shown to inhibit allergen- and PAF-induced broncho constriction.

 Several studies have reported benefit in patients with asthma when using picrorhiza. In a randomized crossover study using laboratory animals, administration of isolated androsin orally or by inhalation prevented bronchial obstruction induced by the inhalation of allergens, platelet activity factors (PAF), histamine, and acetylcholine. It was concluded in this study that asthmatic reactions due to histamine and acetylcholine were not altered by picrorhiza, suggesting that androsin is not a broncholytic agent, but prevents bronchial obstruction. It is suggested that androsin may act by depressing the activity of PAF, which plays a major role in the pathogenesis of bronchial asthma. PAF has been reported to provoke long-term inflammatory responses in the lungs, leading to bronchial hyper-reactivity and subsequent bronchial obstruction. Additionally, histamine release from human polymorphonuclear leucocytes, in vitro, has been reported inhibited by some compounds from picrorhiza that have yet to be identified.Picrorhiza reportedly stabilizes mast cells in vivo, further elucidated by a repeated study in vitro in laboratory animals.This may prove useful as part of an integrative approach in patients with allergic conditions.

 In vivo studies of bronchial obstruction indicate that the drosin constituent of Picrorhiza kurroa prevented allergen- and platelet activating factor-induced bronchial obstruction when given to guinea pigs via inhalant and oral routes. In vitro histamine release was also inhibited by the plant extract.Picrorhiza extract given orally at 25 mg/kg to mice and rats resulted in a concentration-dependent decrease in mast cell degranulation. However, induced bronchospasm was not prevented, indicating a lack of direct post-synaptic histamine receptor blocking activity.

 A one-year clinical study of 20 patients (ages 14-60 years), two with perennial asthma, others with seasonal asthma, was conducted using picrorhiza as a therapeutic agent.The degree of clinical improvement in the patients was measured in terms of reduction in the use of bronchodilators, as evident from the results of pulmonary function tests at regular intervals. The patients had experienced asthma symptoms ranging from five to twenty years. The peak expiratory flow rate (PEFR) was monitored and reported sustained increases for up to twelve months of treatment with picrorhiza. The frequency and severity of asthmatic attacks reduced significantly as treatment progressed. A reduction in bronchodilator use was also observed. One observation of interest is that individuals having specific food allergies developed tolerance to these allergens during the period of treatment, probably due in part to the mast cell stabilization properties of picrorhiza.

 A double-blind, crossover trial with placebo failed to demonstrate significant results, although there was a trend toward improvement in symptoms of asthma.Study design and high dropout rate in this trial may have contributed to the poor results.

  Constipation:Digestion

 Picrorhiza is used in India for people with constipation due to insufficient digestive secretions.

  Hepatic Insult and Damage:

 Numerous animal studies, primarily in rats, have demonstrated that the active constituents of Picrorhiza kurroa are effective at preventing liver toxicity and the subsequent biochemical changes caused by numerous toxic agents. Hepatocytes damaged by exposure to galactosamine, thiocetamide, and carbon tetrachloride were incubated with Picrorhiza constituents. A concentration-dependent restorative effect was observed in regard to normal hepatocyte function.A similar effect was seen when 25 mg/kg/day oral Picrorhiza extract was administered to rats poisoned by aflatoxin B1 exposure. Picrorhiza kurroa significantly prevented the biochemical changes induced by aflatoxin B1.Picrorhiz extract, when given at a dose of 3-12 mg/kg orally for 45 days, was also shown to be effective in reversing ethanol-induced liver damage in rats.In an animal model of hepatic ischemia, rats given Picrorhiza orally at 12 mg/kg daily for 7 days, prior to induced ischemia, demonstrated improved hepatocyte glycogen preservation and reduced apoptosis, compared to control animals.Picrorhiza principals have also shown to be effective in treating Amanita mushroom poisoning in an in vivo animal model.An in vitro study demonstrated Picrorhiza's antioxidant activity by subjecting human Glioma and Hep 3B cells to a hypoxic state. Picrorhiza treatment reduced the cellular damage cause by hypoxia, indicating Picrorhiza constituents may protect against hypoxia/reoxygenation-induced injuries.

  Hepato-protection:

 The hepatoprotective effect of Picrorrhiza kurroa roots have been shown in diverse models of liver injury. The crude extract, and the isolated active principles of the roots, have been shown to protect the liver from various types of drug-induced injury Isolated compounds from P.kurroa have also been shown to have hepatoprotective activity. Picroliv, a specific combination of iridoid glycosides from P. kurroa, has been reported to inhibit drug- induced hepatocarcinogenesis and to prevent the biochemical changes in Wistar rats administered with aflatoxin B1 and phenobarbiton experimentally.

 Similar to milk thistle, picrorhiza may have an effect on liver regeneration. A 1992 study demonstrated stimulation of nucleic acid and protein synthesis in rat liver with oral administration of picrorhiza. The authors stated the results were comparable to milk thistle.Clinical research has validated the efficacy of several plants that support liver health. Basic scientific research has unveiled the mechanisms by which some plants provide their therapeutic effects. Silymarin has been shown to have clinical applications to support various applications of liver health. Picrorhiza kurroa (PK), appears to have similar applications and mechanisms as that of silymarin although there is less clinical data to support it therapeutic use. However, when compared with silymarin, the hepatoprotective effects of Picrorhiza were found to be similar.A galactosamine-induced liver injury study in animals showed a significant reduction in liver lipid content, ALT and AST. In a trial in patients with liver concerns, difference in values of bilirubin, ALT and AST were significant between placebo and PK groups.

 There have been over 15 studies conducted in laboratory animals regarding the effectiveness of standardized picrorhiza as a tool in liver health. Studies report picrorhiza beneficial for the liver, including viral hepatitis, and exposure to hepatotoxic chemical agents, including alcohol and acetaminophen.Another factor in the hepato-protection of picrorhiza may be its anti-inflammatory effects.

 Picrorhiza was evaluated as a hepato-protective agent against ethanol-induced hepatic injury in rats.There was also an effect on specific alcohol-metabolizing enzymes (aldehyde dehydrogenase, 41%; acetaldehyde dehydrogenase, 52%) in rat hepatocytes. The levels of these enzymes were found to be reduced in the cells following alcohol intoxication.

 Several hepatotoxins, including paracetamol and ethynyl estradiol, have a cholestatic effect on the production of bile. Picrorhiza has been reported to reverse acetaminophen and ethynyl estradiol-induced cholestasis, maintaining both bile volume and flow. Milk thistle was tested simultaneously for comparison. Picrorhiza was found to be a more potent choleretic and anticholestatic agent than milk thistle.Ethyl alcohol also produces cholestasis to varying degrees, as indicated by reduction in bile volume, bile salts, and bile acids. Picrorhiza treatment has been reported to restore these altered parameters in a dose-dependent manner.

 In a randomized, double-blind placebo controlled trial in patients diagnosed to have acute viral hepatitis (HBsAg negative), picrorhiza root powder, 375mg three times a day, was given for two weeks.Picrorhiza was reported to significantly decrease lab values of bilirubin, SGOT, and SGPT as compared to placebo. The time in days required for total serum bilirubin to drop to an average value of 2.5mg% was 75.9 days in placebo compared to 27.44 days in the picrorhiza group. Also, the active principles picroside I, catalpol, kutkoside, and kutkoside 1 were tested for the presence of anti-hepatitis B virus surface antigen (anti-HBsAg) like activity in vitro.A promising anti-HBsAg like activity was noted which differed from the classical viral neutralization. Picrorhiza also inhibited purified HBV antigens prepared from healthy HBsAg carriers from binding in vitro.

 As an antioxidant for the liver, picrorhiza is reported to protect against changes in liver and brain glutathione metabolism, improving reduced glutathione levels, and decreasing inhibition of glutathione-S-transferase, glutathione reductase, and glutathione peroxidase.The increased levels of lipid peroxidation products in damaged tissues were also reduced along with the recovery of glutathione metabolism. Also, picrorhiza possess the properties of antioxidants that appear to be mediated through activity like that of superoxide dismutase, metal ion chelators, and xanthine oxidase inhibitors.Picrorhiza does seem to alter cytochrome P-450 enzyme levels. Therefore, caution should be used with medications that are metabolized in the liver.

  Hypoglycemic:

 An extract of picrorhiza was found to lower blood glucose in laboratory animals.Chronic administration of the extract significantly reduced blood sugar in alloxan-induced diabetic rats for 10 days. The extract was also found to reduce the increased blood urea nitrogen and serum lipid peroxides in alloxan-induced diabetic animals and to inhibit the body weight reduction and leukopenia induced by alloxan administration. Further study is required to determine benefits to diabetics.

  Immune system modulation:

 The effect of an ethanolic extract of each drug was studied on delayed type, hypersensitivity, humoral responses to sheep red blood cells, skin allograft rejection, and phagocytic activity of the reticuloendothelial system in mice. Picrorhiza kurroa was found to be a potent immunostimulant of both cell-mediated and humoral immunity.The clinical success in treating vitiligo, a benign autoimmune disease characterized by irregular skin patches without pigmentation, is attributed to the immunomodulating effects of picrorhiza.

 Recently, an ethanolic extract of the leaf of picrorhiza was reported to stimulate cell mediated and humoral components of the immune system including stimulation of phagocytosis.Also, picrorhiza root has reported anti-tumour and anti-carcinogenic activity in laboratory studies.

  Hypoxia:

 Picrorhiza has been reported to protect cells and regulate gene expression during hypoxia and/or re-oxygenation.Picrorhiza reduced the cellular damage caused by hypoxia as revealed by a significant reduction in LDH release compared to untreated controls. These findings suggest that picrorhiza may act as a protective agent against hypoxia and/or re-oxygenation induced injuries by a novel signal transduction pathway to the cells.

  Immunomodulatory Activity:

 P. kurroa is considered to be one of the most promising immunomodulatory agents of herbal origin. Various solvent extracts were screened for their influence on complement mediated haemolysis and on the production of lumino-dependent chemiluminescense by activated human neutrophils. All exhibited dose-dependent inhibitory effects, the methanolic and aqueous extracts being the most potent In an experimental study in mice, the oral administration of Picroliv prior to immunisation .with sheep red blood cells resulted in a significant increase in haemagglutinating antibody titre, plaque-forming cells and delayed hypersensitivity response to SRBC. Picroliv further enhanced the non-specific immune response characterised by an increase in the macrophage migration index.

  Infections:Chronic / Hidden Infection:

 Picrorhiza is used for fever due to all manner of infections.Picroliv (a mixture of iridoid glycosides from the rhizomes of picrorhiza) has been shown to have an immuno-stimulating effect in hamsters, helping prevent infections.

  Inflammation.:

 Apocynin is a constituent of root extracts of picrorhiza and has been reported to possess anti-inflammatory properties in laboratory animals.Apocynin concentration dependently inhibited the formation of thromboxane A2, whereas the release of prostaglandins E2 and F2 alpha was stimulated. Apocynin inhibited arachidonic acid-induced aggregation of bovine platelets, possibly through inhibition of thromboxane formation. Apocynin was found to inhibit neutrophil oxidative burst in vitro without affecting beneficial activities such as chemotaxis, phagocytosis, and intracellular killing of bacteria.

  Musculo-Skeletal:Rheumatoid Arthritis:

 Open-label studies conducted in India show a preliminary benefit for persons with primarily rheumatoid arthritis.

  Viral Hepatitis:

 Studies indicate Picrorhiza extracts may be of therapeutic value in treating viral hepatitis. An in vitro study investigated anti-hepatitis B-like activity of Picrorhiza and found it to have promising anti-hepatitis B surface antigen activity. In a randomized, double-blind, placebo-controlled trial of 33 patients diagnosed with acute viral hepatitis, 375 mg Picrorhiza root powder was given three times daily for two weeks. The treatment group was comprised of 15 patients; the remaining 18 subjects acted as controls and received placebo. Bilirubin, SGOT, and SGPT values were significantly lower in the treatment group, and the time required for bilirubin values to drop to 2.5 mg% was 27.4 days in the treatment group versus 75.9 days for the placebo group.

  Vitiligo:Autoimmune

 Picrorhiza, in preliminary research and in combination with the drug methoxsalen and sun exposure, was reported to hasten recovery in people with vitiligo, compared to using methoxsalen and sun exposure alone.


   Application Case Study:Liver function improvement formulation.

 Details Reference to USPatent 6759061.

  Background:

 The liver is the largest human internal organ. It performs a number of functions, including detoxifying the body. The liver cleanses the body by filtering, or changing the compositions of toxins so that they can be removed from the blood stream, generally at a processing rate of about one liter of blood each minute. Endotoxins, exotoxins, and other wastes are directed to the kidneys or colon. A number of toxins, however, are made up of compounds that are difficult for the liver to filter and remove from the blood stream. These toxins are broken down by various enzymes so that they too may be removed from the body. Accordingly, a properly-functioning liver plays a critical role in determining a person's overall health.

 It would be desirable to develop a food supplement which additionally improves the functioning of the human liver by promoting the body's ability to cleanse and detoxify the liver.

  Invention Field:

 The present invention relates generally to a liver function improvement formulation. More particularly, the invention is directed to a two-part organic food supplement formulation that improves the function of the human liver, by supporting the body's process for cleansing and detoxifying the liver.

  Preferred Embodiment:

 The organic formulation according to the present invention is useful as a food supplement to promote general health, and additionally is particularly useful for cleansing and detoxifying the liver for improved functionality.

 The present invention is directed to a food supplement formulation, comprising selenium; milk thistle seed; phosphatidyl choline; dandelion root; l-methionine; l-taurine; n-acetyl-cysteine; alpha lipoic acid; artichoke leaf; green tea leaf; turmeric root; belleric myrobalan fruit; boerhavia diffusa; eclipta alba; wedelolactones; tinospora cordifolia; andrographis paniculata; and picrorhiza kurroa. The inventive food supplement formulation is administered in two parts. The first part is generally administered in the morning, while the second part is generally administered in the evening.

  Selenium is a well-known component of several human enzymes that protects the body's arteries and cell membranes from damage from free radicals. Preferably, the concentration of selenium in part 1 of the inventive formulation may be about 0.1 weight percent.

  Milk thistle seed is a bioflavonoid complex which exerts a powerful anti-oxidant effect, and interrupts the enterohepatic recirculation of toxins in the human liver. The concentration of milk thistle seed as a component of part 1 of the inventive formulation preferably may be about 25 weight percent.

  Phosphatidyl choline is necessary for the body's production of acetycholine which assists the transmission of nerve impulses and breaks down fatty deposits in the blood stream. Phosphatidyl choline may be present in part 1 of the inventive formulation at a concentration preferably of about 15 weight percent.

  Dandelion root is a well-known substance that stimulates the production of bile in the liver and the secretion of bile from the gallbladder, and is also a diuretic. Dandelion root may be present in part 1 of the inventive formulation at a concentration preferably of about 10 weight percent.

  l-methionine is an amino acid and chelation agent that aids the break-down of fat in the human liver and arteries. The concentration of l-methionine as a component of part 1 of the inventive formulation preferably is about 10 weight percent.

  l-taurine is an amino acid that assists in the production of bile, aids the absorption of fat-soluble vitamins, and supports healthy serum cholesterol levels. l-taurine may be present in part 1 of the inventive formulation at a concentration preferably of about 10 weight percent.

  N-acetyl-cysteine is an altered form of the amino acid cysteine. N-acetyl-cysteine assists the body in breakingdown mucus and synthesizing glutathione, an important antioxidant. N-acetyl-cysteine may be present in part 1 of the inventive formulation at a concentration preferably of about 10 weight percent.

  Alpha lipoic acid is a substance necessary for human metabolism, and additionally acts as an antioxidant when present in the human body in sufficient quantity. Preferably, the concentration of alpha lipoic acid as a component of part 1 of the inventive formulation may be about 5 weight percent.

  Artichoke leaf is a well-known vegetable-derived component useful for the body's process of breaking-down fat, and for improving the production and flow of bile. Artichoke leaf may be present in part 1 of the inventive formulation at a concentration preferably of about 5 weight percent.

  Green tea leaf contains polyphenols which are powerful antioxidants that additionally can increase the removal of cholesterol from the blood by a receptor mediated mechanism. Green tea leaf may be present in part 1 of the inventive formulation at a concentration preferably of about 5 weight percent.

  Turmeric root is an antioxidant, and is reportedly useful for lowering cholesterol levels in the blood stream. The concentration of turmeric root in part 1 of the inventive formulation may be preferably about 5 weight percent.

  Belleric myrobalan fruit is a natural product from the fruit of the terminalia bellerica plant, known to be useful for improving digestion, assisting in the body's nutrient absorption, and aiding the body's metabolic processes. Belleric myrobalan fruit may be present as a component of part 2 of the inventive formulation at a concentration preferably of about 20 weight percent.

  Boerhavia diffusa is a plant-derived material known to be useful as a diuretic and anti-inflammatory compound. Boerhavia diffusa may be present as a component of part 2 of the inventive formulation at a concentration preferably of about 20 weight percent.

  Eclipta alba is an herb used to promote bile flow and stimulate digestion. The concentration of eclipta alba as a component of part 2 of the inventive formulation may be preferably about 19 weight percent.

  Wedelolactones is an extract from the eclipta alba plant, useful generally as an anti inflammatory agent. Wedelolactones may be present as a component of part 2 of the inventive formulation at a concentration preferably of about 1 weight percent.

  Tinospora cordifolia is effective in inhibiting the growth of bacteria and enhancing immune resistance. Tinospora cordifolia may be present as a component of part 2 of the inventive formulation at a concentration preferably of about 20 weight percent.

  Andrographis paniculata is a plant extract that enhances the body's immune system, and reportedly has been particularly effective for lessening the symptoms associated with the common cold. Preferably, andrographis paniculata may be present as a component of part 2 of the inventive formulation at a concentration preferably of about 10 weight percent.

 Finally,  Picrorhiza kurroa is a material widely used to treat dyspepsia and chronic diarrhea, and is effective as an antioxidant. Picrorhiza kurroa may be present as a component of part 2 of the inventive formulation at a concentration preferably of about 10 weight percent.

 The aforementioned ingredients may be combined into parts 1 or 2 of the inventive formulation. Thereafter, the ingredients are mixed by conventional means to form parts 1 and 2 of the invention. Each of these parts may then be formed by conventional means into tablets for subsequent oral administration. Alternatively, the ingredients may be combined and placed in gelatin capsules, thereby forming separate capsules containing the part 1 and part 2 mixtures. The inventive formulation may also contain conventional food supplement adjuvants, fillers, and/or extenders such as, for example, rice flour.

 Conveniently, the inventive food supplement formulation may be taken in separate oral dosages; part 1 in the morning, and part 2 in the evening. The dosage rates for parts 1 and 2 may vary over wide limits from about 100 mg each to about 5,000 mg each. Preferably, parts 1 and 2 are administered in dosages of about 1,000 mg each.

 This invention is more easily comprehended by reference to the specific embodiments recited hereinabove which are representative of the invention. It must be understood, however, that the specific embodiments are provided only for the purpose of illustration, and that the invention may be practiced otherwise than as specifically illustrated without departing from its spirit and scope.


   Dosage,Administrations and Safety:

  Adult Dosage Range: 500mg - 2g/day or 400 to 1500 mg/day of the dried root.with doses up to 3.5 g/day sometimes being recommended for fevers.250mg (standardized extract), 2 to 4 times daily.Tincture: 2 to 4 ml daily.
  Most Common Dosage: 250mg (standardized extract), 2 times daily.Tincture: 2 ml daily.
 1-4mL/day of 1:2 extract
  Root powder: 300 - 500 mg. b.i.d. / t.i.d. 2 - 3 weeks for viral hepatitis.1 - 2 gms. M.S. for laxative effect
  Standardization: The most current available medical and scientific literature indicates that this dietary supplement should be standardized to 4%-10% kutkin.
 3-4 gm of drug is generally given as antiperiodic and 0.6-1.2 gm as bitter tonic. Typical adult dosage is 400 to 1500 mg/day, with dosages up to 3.5 g/day sometimes being recommended for fevers
 Between 400 and 1,500 mg of powdered, encapsulated picrorhiza per day has been recommended. One author considers this equivalent to the use of 1~!2 ml of fluid extract twice per day.Picrorhiza tastes quite bitter. Combining with ginger root powder capsules or taking as tea can improve palatability.

  Side effects or interactions:

 Loose stools and colic have been reported when unprepared picrorhiza rhizomes are used as medicine. However, extracts in alcohol have shown much less tendency to cause such effects.19 No other adverse effects have been reported with picrorhiza. Although the use of the herb is not discouraged in India during pregnancy and breast-feeding, there is little information to determine the safety of the herb during these times.

  Caution:

 In sensitive individuals high doses may cause diarrhea,flatulence and griping (due to cucurbitacins),skin rash
 Some people find the bitterness intolerable
 Cautions Contraindicated in Spleen/Stomach Deficiency
 Contraindicated in pregnancy
 Toxicity Relatively safe for long term use
 General:Picrorhiza is reported safe in recommended dosages.
 Health Conditions:Based on pharmacology, use with caution in individuals with bleeding disorders.
 Pregnancy/Breast-Feeding:If pregnant or nursing, consult a physician before use.
 Age Limitations:Do not use in children under 2 years of age unless recommended by a physician.

  Clinical trials:

 Picrorhiza kurroa (P.kurroa), a known hepatoprotective plant, has been studied in experimental and clinical situations.In a randomised, double-blind placebo controlled trial in patients diagnosed to have acute viral hepatitis (HBsAg negative), P. kurroa root powder 375 mg three times a day was given for 2 weeks (n = 15) or a matching placebo (n = 18) was given. Difference in values of bilirubin, SGOT and SGPT was significant between placebo and P.kurroa groups. The time in days required for total serum bilirubin to drop to average value of 2.5 mg% was 75.9 days in placebo as against 27.44 days in P.kurroa group.

  Toxicity and Safety:

 Picrorhiza is generally regarded as safe when taken in the recommended doses; however, mild side effects such as loose stools and colic pains occur when unprepared Picrorhiza rhizomes are used.Picrorhiza is not readily water-soluble and is therefore not usually taken as a tea. While it is ethanol soluble, the bitter taste makes tinctures unpalatable, so it is therefore usually administered as a standardized (4% kutkin) encapsulated powder extract. Typical adult dosage is 400 to 1500 mg/day, with dosages up to 3.5 g/day sometimes being recommended for fevers. Picrorhiza root extracts are widely used with no adverse effects having been reported. Safety in young children or those with severe liver or kidney disease is not known. The [LD50] of kutkin is greater than 2600 mg/kg in rats with no data available for humans.


  Scientific References:

  1.What is Picrorrhiza Root and it's major application?