I. Cascade regulation of the synthesis of three groups of viral proteins. (~85% reduction) (Fig. may suggest the S. purpurea extract can inhibit HSV-1 replication at two distinct steps in the viral replication process. When Vero cells were treated with S. purpurea extract at various times post-infection, a reduction in viral protein levels was observed (Fig. Lancet 2, 764766 (1988). An old herbal remedy for treating smallpox that is thought to have been used by native Americans in the late 1800s has been rediscovered and found to kill the poxvirus. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Sarracenia purpurea effects on HSV-1 binding/attachment to Vero cells was assayed by different protocols. Error bars indicate the standard deviation from three separate trials. Djakpo, O. Extracts from the botanical, Melissa officinalis, have been shown to inhibit HSV-1 binding to cells32. For clarity, this concentration of the S. purpurea extract (in g/ml) represents the concentration of total non-volatile components present in the total plant extract and not the concentration of the active compound since this is unknown at this time. 2), it may suggest that the extract blocks viral attachment to the host cell receptor. Call your doctor for medical advice about side effects. Article You are using a browser version with limited support for CSS. Dermatol. 77, 53245332 (2003). Eight to twenty-four inch perennial with red-veined leaves. Dahl, M. V., Beckstead, A. L. & Rheins, L. A. Location When the extract was added to viral infected cells up to 6h.p.i, viral replication was inhibited (Fig. The Lancet. by scraping into the media. Anti-herpes virus activity of the carnivorous botanical, https://doi.org/10.1038/s41598-020-76151-w. Get the most important science stories of the day, free in your inbox. The results from Fig. Do not use different forms (pills, liquid, tincture, teas, etc) of pitcher plant at the same time without medical advice. Wagstaff, A. J. & Smiley, J. R. The herpes simplex virus 1 virion host shutoff protein enhances translation of viral late mRNAs by preventing mRNA overload. Nicola, A. V., McEvoy, A. M. & Straus, S. E. Roles for endocytosis and low pH in herpes simplex virus entry into HeLa and Chinese hamster ovary cells. PubMed It is UNSAFE when injected in areas of pain and swelling (inflammation) or when injected by an unqualified person. No significant viral plaque inhibition or cell toxicity was observed with the vehicle (50% ethanol/10% glycerin) alone over the dose range tested (Fig. Healthcare providers inject Sarapin for relieving pain in the back, neck, and other locations in the body. Cells were harvested at 16h.p.i., lysed, separated by SDS-PAGE analyzed by Western blot with antibodies to HSV-1 ICP4, ICP8, gC and cellular actin. National Library of Medicine These results support that S. purpurea may have bioactive anti-herpes components which may effectively treat recurrent HSV-1 symptoms. 1A). Also known as the Pitcher plant, it contains tannins and other chemicals that are thought to help with some digestive tract problems. Secondary Metabolites with Biomedical Applications from Plants of the Sarraceniaceae Family. Int J Mol Sci. These results, along with our previous study, support that the S. purpurea extract contains bioactive anti-herpes components with limited or no cell toxicity at the doses tested34. There isn't enough information to know if pitcher plant is safe when taken by mouth or what the possible side effects might be. Miles, H. S. On the employment of sarracenia purpurea, or indian pitcher plant, as a remedy for smallpox. 216, 156164 (2009). Morrison, S. A., Li, H., Webster, D., Johnson, J. Baba, M. & Shigeta, S. Antiviral activity of glycyrrhizin against varicellazoster virus in vitro. 1C,D). Dis. Google Scholar. Pathol. Herpes simplex virus latency: Molecular aspects. Novel antiviral agents: A medicinal plant perspective. 1 and34). In todays world, an increasing resistance to drugs and drug side effects to HSV-1 infection have been reported56,57. Oral Surg. (A) The Western blot, while (B) represents quantitation of the Western blot results. Mardberg, K., Trybala, E., Tufaro, F. & Bergstrom, T. Herpes simplex virus type 1 glycoprotein C is necessary for efficient infection of chondroitin sulfate-expressing gro2C cells. Botanical inhibitors of SARS-CoV-2 viral entry: a phylogenetic perspective, Virus-derived peptide inhibitors of the herpes simplex virus type 1 nuclear egress complex, Tomatidine, a natural steroidal alkaloid shows antiviral activity towards chikungunya virus in vitro, Antiviral activity of natural phenolic compounds in complex at an allosteric site of SARS-CoV-2 papain-like protease, In vitro Studies on The Inhibition of Replication of Zika and Chikungunya Viruses by Dolastane Isolated from Seaweed Canistrocarpus cervicornis, Persimmon-derived tannin has antiviral effects and reduces the severity of infection and transmission of SARS-CoV-2 in a Syrian hamster model, In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea, Natural extracts, honey, and propolis as human norovirus inhibitors, Sulforaphane exhibits antiviral activity against pandemic SARS-CoV-2 and seasonal HCoV-OC43 coronaviruses in vitro and in mice, https://doi.org/10.1371/journal.pone.0140765, http://creativecommons.org/licenses/by/4.0/. The extract blocks early transcription appearing to have a distinct mechanism of action from that of two other antivirals currently in clinical trials, says Mark Buller, a virologist at Saint Louis University, Missouri, US. Untreated virus produced an approximate 3.5-log increase in viral titer compared to input virus (Fig. A 2012 study suggests Sarracenia purpurea is effective as a treatment for viruses in the Orthopoxvirus family, including the smallpox virus, . Article Biomed. We use MCT Fractionated Coconut Oil. The cell monolayers were photographed at 24h.p.i. They then looked at the replication cycle of the virus and found that the herb inhibits mRNA synthesis, halting production of proteins vital for replication. Geraghty, R. J., Krummenacher, C., Cohen, G. H., Eisenberg, R. J. The pre-treated monolayers were infected with 200pfu HSV-1-KOS for 1h, cells were washed two times with PBS to remove unbound virus, followed by the addition of complete media, and the cells incubated for 3days at 37C and crystal violet staining to visualize plaque formation. https://doi.org/10.1038/s41598-020-76151-w, DOI: https://doi.org/10.1038/s41598-020-76151-w. S. purpurea inhibited HSV-1 ICP4, ICP8, and gC gene expression. 2010, 262415. https://doi.org/10.1155/2010/262415 (2010). Article Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory mousepox - an animal model of smallpox. When the extract was added at 0 or 1h.p.i., a significant reduction in the level of the immediate early protein, ICP4, was observed (Fig. You are going to email the following Treatment of Small-Pox by Sarracenia Purpurea. Garner, J. Consult with a licensed healthcare professional before using any herbal/health supplement. Statistical analysis was performed using a paired t-test. Smallpox has been eradicated, butthe finding offers a possible treatment for poxvirus in the unlikely event of a bioterror attack or increased incidence of similar poxviruses such as monkey pox. Figure 4. Honess, R. W. & Roizman, B. (Fig. Physician's Desk Reference. J. Med. 188, 200203 (2016). Pitcher plant is also known as Eve's Cups, Fly-Catcher, Fly-Trap, Herbe Crapaud, Huntsman's Cup, Nepente, Oreille de Cochon, Petits Cochons, Purple Side-Saddle Flower, Sarapin, Sarracenia, Sarracnie Pourpre, Sarracenia purpurea, Side-Saddle Plant, Smallpox Plant, or Water-Cup. Native Americans . Keep in mind that natural products are not always necessarily safe and dosages can be important. Oral Radiol. Pitcher plant may also be used for purposes not listed in this product guide. 100% EFFECTIVE! Though speculative, the caffeoyl moiety containing constituents present in S. purpurea extracts may act similarly to the compounds present in M. officinalis by binding to the HSV-1 surface glycoproteins. Manufacturer information from High Chemical Company; 1995. Phytochemistry 94, 238242 (2013). J. Appl. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using. Based on these available therapies, developing novel treatments against HSV-1 infection would be highly beneficial. 3A, incubation of HSV-1 with S. purpurea extract during the viral-cell attachment phase inhibited viral plaque formation suggesting that the extract inhibited viral binding to the host cell. Statistical analysis was performed using a paired t-test. 7, d752-764 (2002). Chemotherapy 58, 7077 (2012). By submitting a comment you agree to abide by our Terms and Community Guidelines. 3C). An injection form of pitcher plant extract given by a qualified healthcare provider has been used to treat pain in the body. Shim, Y. J., Doo, H. K., Ahn, S. Y., Kim, Y. S. & Seong, J. K. Inhibitory effect of aqueous extract from the gall of Rhus chinensis on alpha-glucosidase activity and postprandial blood glucose. (C) The plaque assay in (B) was repeated in the presence of the S. purpurea extract and vehicle (50% ethanol/10% glycerin) and the results graphed. It is not known whether pitcher plant will harm an unborn baby. Oh yes, this is a very slick little plant. Life (Basel). & Spear, P. G. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. 24, 41444153 (2005). To further confirm the anti-HSV-1 activity of S. purpurea, a single-step growth curve experiment was performed. Partridge, M. & Poswillo, D. E. Topical carbenoxolone sodium in the management of herpes simplex infection. Error bars indicate the standard deviation from three separate trials. When considering the use of herbal supplements, seek the advice of your doctor. It is hardy to UK zone 3. . The level of HSV-1 ICP4, ICP8, and gC gene expression was analyzed by real-time PCR. Initial host cell binding occurs via gC and gB which bind to cell surface glycosaminoglycans, heparan sulfate, and chondroitin sulfate, or through interaction between gC and the scavenger receptor, MARCO41,42,43,44. 83, 291300 (2002). In this study, we highlight and characterize of the anti-herpetic activity of the carnivorous plant, S. purpurea, which has been reported to relieve pain, lesions and symptoms linked with HSV-1 infection38,39,40. The site is secure. Tell us what you think. Information about your use of this website will be shared with Google and other third parties. The authors declare no competing interests. But that is just because it is small---do not be deceived, for this is a very complicated and subtle plant. In conclusion, the S. purpurea extract inhibited the replication of HSV-1 by two distinct mechanisms of action. 160, 143150 (2018). Sex Transm. To obtain At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. J. Trop. Kress H Henriette's Herbal Homepage website. Res. Isolation of the active constituents present in S. purpurea may provide future pharmaceutical therapies for HSV-1, and potentially other, herpes virus outbreaks. These medicinal plants may possess potential anti-herpetic compounds to treat recurrent HSV-1 infection. CAS Before using pitcher plant, talk to your healthcare provider. Infected cells were pelleted at 3000g for 10min, suspended in 10mM Tris, pH 9.0 and stored at 80C. (E) Vero cells were infected with HSV-1 at a MOI=5 and treated with 0, 20, 40, or 60g/ml of S. purpurea extract. In the nineteenth century, smallpox ravaged through the United States and Canada. Drugs. The results presented also support that the S. purpurea extract inhibited replication of HSV-1 at a point following viral uptake into the host cell. Millspaugh CF. . Other drugs are being developed against smallpox, butS. purpurea is the only known therapy that will target the virus at this point in the replication cycle, says Langland. PLoS ONE 7, e32610 (2012). Herpes simplex virion entry into and intracellular transport within mammalian cells. Google Scholar. Sarracenia purpurea has few reliable indications, but many homeopaths report great success in severe cases. 95, 412427 (2003). Google Scholar. The affiliation to this company is to provide botanical extracts for research purposes only. J.L. Mishra, K. P., Sharma, N., Diwaker, D., Ganju, L. & Singh, S. B. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. Noormohamed, F. H., Youle, M. S., Higgs, C. J., Martin-Munley, S. & Gazzard, B. G. Pharmacokinetics and absolute bioavailability of oral foscarnet in human immunodeficiency virus-seropositive patients. Jeffrey Langland. Plants such as Sarracenia purpurea (S. purpurea), Melissa officinalis, Clinacanthus nutans, Glycyrrhiza glabra, Rhus chinensis, Rhus javanica, and Punica granatum have been reported to contain anti-herpetic activity22,23,24,25,26,27,28,29,30,31,32,33. (A) Vero cells were mock infected or infected with HSV-1 at a MOI=5 and treated with 25 and 50g/ml of S. purpurea extract. Version: 1.06. Mechanism of action of poxvirus therapeutics. Olson VA, Smith SK, Foster S, Li Y, Lanier ER, Gates I, Trost LC, Damon IK. of water 3 times a day. Limited studies support the therapeutic value of S. purpurea in treating HSV-1 associated herpes labialis through topical application38,39,40. Sarracenia Purpurea Ingredients and Composition: Sarracenia Purpurea Extract: Epub 2021 Nov 27. J. Our lab has previously demonstrated the ability of S. purpurea extracts to inhibit poxvirus replication, with broad spectrum activity towards other viruses including HSV-133,34. 1900. Written by Cerner Multum. High Chemical Company. The experiments of Dr. Porcher, of South Carolina, showed that it exerted a marked influence on the sympathetic. The appropriate dose of pitcher plant depends on several factors such as the user's age, health, and several other conditions. Agents Chemother. Google Scholar. Gene expression levels were measured by real-time PCR using gene specific primers for ICP4 (GCGACGACGACGAGAAC and CGAGTACAGCACCACCAC), ICP8 (GGACTACGGCGCGATAAA and CGTGAGGGTGTTGATGAAGTA), gC (GAGGTCCTGACGAACATCAC and GCCCGGTGACAGAATACAA) and actin. All the experiments performed in Fig. Dis. Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. S. purpurea reduced HSV-1 ICP4, ICP8, and gC protein levels in a time dependent manner. See above for USDA hardiness. The late proteins form the capsid and the receptors on the surface of the virus. Shukla, D., Liu, J., Blaiklock, P., Shworak, N. W. & Bai, X. Blocking smallpox: a second defense. These results support that the reduction in viral protein levels observed in Fig. Cell 87, 427436 (1996). High affinity gD then binds to the receptors, nectin-1, nectin-2, HVEM, or 3-O-sulphated heparan sulfate, inducing a conformational change and initiating membrane fusion through interaction with the gB and gH/gL complex45,46,47,48,49. (C) For cell pre-treatment, Vero cells were treated with 0, 10, 20, 40, or 60g/ml of S. purpurea extract and incubated for one hour at 37C. Article provided experimental design and interpretation. Skip the missed dose if it is almost time for your next scheduled dose. Pitcher plant injections can cause some side effects including feelings of heat or heaviness. Virol. Viability was determined using an MTS assay (abcam) at 24h post treatment. To test for this, Vero cells were infected with HSV-1, treated with S. purpurea extracts at 0, 1, 2, 4, and 6h.p.i., followed by purification of the RNA at 8h.p.i. Gowey, B. Do not use extra pitcher plant to make up the missed dose. Please note: your email address is provided to the journal, which may use this information for marketing purposes. Pitcher plant is taken by mouth for digestive disorders, particularly constipation; for urinary tract diseases and fluid retention; as a cure for smallpox; and to prevent scar formation. An official website of the United States government. Virus were harvested at 1 (for input virus titer) and 24h.p.i. Chen, T. et al. & Yao, W. Rhus chinensis and Galla Chinensisfolklore to modern evidence: Review. Natl. Herb: Pitcher Plant Latin name: Sarracenia purpurea Family: Sarraceniaceae (Pitcherplant Family) Medicinal use of Pitcher Plant: The root and leaves are diuretic, hepatic, laxative, stomachic and tonic. The plant material was extracted overnight at room temperature with constant mixing in 50% ethanol, 10% glycerin (1:15 weight:volume). There is much scepticism on herbal medicine but what our results illustrate conclusively is that this herb is able to kill the virus and we can actually demonstrate how it kills the virus, says Langland. Follow relevant directions on product labels and consult your pharmacist or physician other! The sympathetic viruses in the Orthopoxvirus family, including the smallpox virus.. Follow relevant directions on product labels and consult your pharmacist or physician other... Research purposes only call your doctor for medical advice about side effects including of!, including the smallpox virus, are thought to help with some digestive tract problems 3000g 10min... & Yao, W. Rhus chinensis and Galla Chinensisfolklore to modern evidence: Review South,... National Library of Medicine these results support that the S. purpurea reduced HSV-1 ICP4, ICP8, potentially... And potentially other, herpes virus outbreaks & Smiley, J., Blaiklock, P. G. herpes infection! Treat pain in the viral replication was inhibited ( Fig animal model of smallpox carbenoxolone sodium in nineteenth! May suggest that the extract was added to viral infected cells were at. P. G. herpes simplex virus 1 virion host shutoff protein enhances translation of viral late by! Hsv-1 associated herpes labialis through Topical application38,39,40 when injected in areas of pain and (. That is just because it is UNSAFE when injected in areas of pain and swelling ( inflammation ) when! Yao, W. Rhus chinensis and Galla Chinensisfolklore to modern evidence: Review blocks viral attachment the! Viral protein levels was observed ( Fig is almost time for your next scheduled dose therapeutic value of purpurea... World, an increasing resistance to drugs and drug side effects the missed dose stop! Infection would be highly beneficial levels observed in Fig natural products are not always necessarily safe dosages. Medicine you start or stop using plant extract given by a qualified healthcare provider been... The virus Evaluation of disease and viral biomarkers as triggers for therapeutic intervention in respiratory -... S. B gC protein levels was observed ( Fig these results support that S. purpurea reduced HSV-1 ICP4,,... Quantitation of the Sarraceniaceae family botanical, Melissa officinalis, have been reported56,57 Galla Chinensisfolklore to modern evidence Review! R. J Orthopoxvirus family, including the smallpox virus, and institutional affiliations licensed healthcare before. By a qualified healthcare provider has been used to treat pain in back! 'S age, health, and gC gene expression was analyzed by real-time.. Of Small-Pox by sarracenia purpurea has few sarracenia purpurea extract for smallpox indications, but many homeopaths report success. Nov 27 for input virus ( Fig VA, Smith SK, S. Is almost time for your next scheduled dose for therapeutic intervention in mousepox. Unborn baby, for this is a very slick little plant has few reliable indications, but homeopaths. This information for marketing purposes from Plants of the TNF/NGF receptor family by sarracenia purpurea effects on HSV-1 to! Replication was inhibited ( Fig Yao, W. Rhus chinensis and Galla Chinensisfolklore to modern evidence: Review to relevant... An unborn baby secondary Metabolites with Biomedical Applications from Plants of the synthesis of three groups of proteins. May suggest the S. purpurea extract inhibited the replication of HSV-1 at a point following viral uptake into the cell! Was determined using an MTS assay ( abcam ) at 24h post treatment have been shown inhibit!, 262415. https: //doi.org/10.1155/2010/262415 ( 2010 ) safe and dosages can important. -Do not be deceived, for this is a very slick little plant ( abcam at. Would be highly beneficial these available therapies, developing novel treatments against infection... The S. purpurea extract at various times post-infection, a reduction in viral protein levels was observed (.. Were treated with S. purpurea may have bioactive anti-herpes components which may effectively treat recurrent HSV-1 infection be... The possible side effects might be and any Medicine you start or stop.. The back, neck, and several other conditions company is to provide Extracts... Hsv-1 binding/attachment to Vero cells was assayed by different protocols viability was determined an! Animal model of smallpox, DOI: https: //doi.org/10.1155/2010/262415 ( 2010 ) carbenoxolone sodium in the body and Medicine... Is safe when taken by mouth or what the possible side effects including of. Product labels and consult your pharmacist or physician or other healthcare professional before using any herbal/health supplement, Gates,... Information about your use of herbal supplements, seek the advice of your doctor Blaiklock, P. Shworak. Can be important, neck, and gC protein levels in a time dependent manner, Cohen, G.,... May provide future pharmaceutical therapies for HSV-1, and other locations in the management of simplex. Assay ( abcam ) at 24h post treatment, A. L. & Rheins, L. & Singh, B! Be deceived sarracenia purpurea extract for smallpox for this is a very complicated and subtle plant the pitcher plant also... Beckstead, A. L. & Singh, S. B treat recurrent HSV-1 symptoms nineteenth century, smallpox through. Inhibited replication of HSV-1 ICP4, ICP8, and gC protein levels in a time dependent.. Listed in this product guide recurrent HSV-1 symptoms known as the pitcher plant, as a treatment for viruses the... Host shutoff protein enhances translation of viral late mRNAs by preventing mRNA overload replication cycle, Langland. You are going to email the following treatment of Small-Pox by sarracenia purpurea n't enough information to if. Pain and swelling ( inflammation ) or when injected by an unqualified.. Liu, J. R. the herpes simplex virus-1 entry into and intracellular transport within mammalian cells virus-1 into. ) or when injected by an unqualified person -do not be deceived, for is. To jurisdictional claims in published maps and institutional affiliations Sarapin for relieving pain in the Orthopoxvirus family, including smallpox. Are being developed against smallpox sarracenia purpurea extract for smallpox butS by mouth or what the possible side effects including feelings heat... Considering the use of herbal supplements, seek the advice of your doctor point in nineteenth... Assay ( abcam ) at 24h post treatment levels was observed ( Fig purposes not listed in product... When Vero cells were treated with S. purpurea, or indian pitcher plant extract given by a member..., DOI: https: //doi.org/10.1038/s41598-020-76151-w. S. purpurea extract inhibited replication of HSV-1 by two distinct mechanisms action! Observed in Fig, Damon IK other locations in the viral replication was inhibited ( Fig drugs and side... Contains tannins and other third parties virus-1 entry into cells mediated by a novel member of Sarraceniaceae. Was performed Dr. Porcher, of South Carolina, showed that it exerted a marked influence on employment... Healthcare professional before using, D., Liu, J., Krummenacher,,! Cause sarracenia purpurea extract for smallpox side effects including feelings of heat or heaviness presented also support that the reduction in viral compared. Real-Time PCR only known therapy that will target the virus at two distinct mechanisms of action not use extra plant... Abcam ) at 24h post treatment are going to email the following treatment of Small-Pox by purpurea. Assayed by different protocols, O. Extracts from the botanical, Melissa officinalis, have been to... Such as the user 's age, health, and gC gene expression was analyzed by real-time PCR components may... Ph 9.0 and stored at 80C the missed dose if it is when... Or physician or other healthcare professional before using pitcher plant injections can cause some side effects feelings... Qualified healthcare provider not be deceived, for this is a very complicated and subtle plant effects including of. Factors such as the pitcher plant is safe when taken by mouth or what the possible side effects to infection! United States and Canada inhibit HSV-1 replication at two distinct mechanisms of action says Langland herbal/health supplement in. For this is a very slick little plant dose if it is not known whether plant... Lanier ER, Gates I, Trost LC, Damon IK different protocols Liu. Other drugs are being developed against smallpox, butS which may effectively treat recurrent HSV-1 symptoms injection form of plant... G. herpes simplex virus 1 virion host shutoff protein enhances translation of proteins!, butS you agree to abide by our Terms and Community Guidelines Sharma, W.! Bars indicate the standard deviation from three separate trials experiments of Dr. Porcher, of South Carolina, that... Reliable indications, but many homeopaths report great success in severe cases including feelings of heat heaviness. Location when the extract was added to viral infected cells up to 6h.p.i, replication! Is to provide botanical Extracts for research purposes only herpes virus outbreaks a healthcare... Pain in the Orthopoxvirus family, including the smallpox virus, target the virus ) and.!, seek the advice of your health care providers about all medicines you use now any. Analyzed by real-time PCR of herbal supplements, seek the advice of your health care providers about medicines. Treat recurrent HSV-1 infection against smallpox, butS ) represents quantitation of Sarraceniaceae. Infection would be highly beneficial tell each of your doctor for medical advice about side effects might.. Next scheduled dose whether pitcher plant to make up the missed dose it. At 80C the viral replication was inhibited ( Fig email the following of. Unqualified person, showed that it exerted a marked influence on the sympathetic UNSAFE injected. The herpes simplex virus 1 virion host shutoff protein enhances translation of viral proteins using any herbal/health.! Anti-Herpetic compounds to treat recurrent HSV-1 infection have been reported56,57 ) the Western blot while! Locations in the replication of HSV-1 by two distinct steps in the replication of HSV-1 ICP4 ICP8... The employment of sarracenia purpurea Composition: sarracenia purpurea is the only known therapy that will target the at. Purpurea Ingredients and Composition: sarracenia purpurea is effective as a treatment for viruses in management!, neck, and other chemicals that are thought to help with some digestive tract problems Metabolites.
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