2018;178:12431. Indirubin potentiates ciprofloxacin activity in the NorA efflux pump of Staphylococcus aureus. J Am Soc Nephrol. Zhao [20] found that indigo and indirubin, the main components of indigo naturalis, could effectively scavenge superoxide anion. The manufacturing process of Indigo naturalis. Intern Med. Initially, indigo naturalis was used as a primitive dye in ancient India and then introduced into China through Persia [1]. It helps in curing convulsion. Cancer. BMC Complement Altern Med. Cheng, H.-M., Wu, Y.-C., Wang, Q., Song, M., Wu, J., Chen, D., & Huang, C. C. (2017, September 2). In Natural History, Pliny mentions that indigo naturalis from the East was used by ancient Romans as paint, applied around the eyes as a cosmetic, or used as medicine, to promote wound healing. This article will discuss the herbal remedies that currently have the most robust evidence base as treatments for psoriasis. Background: It has been reported in the Chinese literature that indigo naturalis exhibits potential antipsoriatic effects in systemic therapy. Servier Presents Transformational Data from Pivotal Phase 3 INDIGO The discovery of these bioactivities provided positive support for the clinical applications of indigo naturalis. Indirubin Treatment of Lipopolysaccharide-Induced Mastitis in a Mouse Model and Activity in Mouse Mammary Epithelial Cells. 2017;173:2333. PubMed Central The organic components can be divided into the following categories [6, 9, 10]. 2007;13:2539. Indigo naturalis is a blue dye in ancient, as well as an extensive used traditional Chinese medicine. Provided by the Springer Nature SharedIt content-sharing initiative. Anti-psoriatic effects of indigo naturalis on the proliferation and differentiation of keratinocytes with indirubin as the active component. Therefore, researchers should also focus on the control of inorganic content in indigo naturalis, except for the control of organic matter content. The material was identified by the authors. Background: Clinical trials have proven that indigo naturalis is a candidate drug for treating ulcerative colitis (UC), but its therapeutic mechanism is still unclear. Indigo dye is a derivative of indican, a glucosideChanayatht 2002, Duke 1985 component of B. cusia and numerous Indigofera species. Pediatr Dermatol. Indospicine is also hepatotoxic.Hegarty 1988, Liener 1980 In animals, indospicine causes cleft palate and embryolethality.Evans 1989, Fletcher 2015 Indigofera endacaphylla (creeping indigo) has caused livestock poisonings and deaths.Simon 1984. People have used herbs to treat skin conditions for centuries, and recent research has supported the idea that some herbal treatments may improve psoriasis symptoms. Antiviral Res. Zhang A, Qu Y, Zhang B, et al. Yu H, Li TN, Ran Q, et al. 2007;85:126370. Reducing the damage of CCL4 to liver tissue and protecting the liver. From natural dye to herbal medicine: a systematic review of chemical constituents, pharmacological effects and clinical applications of indigo naturalis. 2004;67:16774. Chang HN, Huang ST, Yeh YC, et al. Indican is enzymatically converted to blue indigotin.Chanayatht 2002, Simon 1984 This colorfast dye is combined with stabilizers and other compounds to produce a wide range of colorants. Meanwhile, it could interfere with protein modification induced by a lipid peroxidation product 4-hydroxy-2-nonenal (HNE), and protect keratinocytes from the electrophilic attack of HNE. WQ M. K, Y., X, T., et al. In the absence of light, indigo can have antibacterial effects on Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus vulgaris, and Candida albicans (minimum inhibitory concentration [MIC]=240m). Clinical trials have shown that the curative effect of IN for psoriasis and . 2020;101:4928. At present, researches on the quality control of indigo naturalis are mainly focused on the organic compounds such as indigo, indirubin and tryptamine. We avoid using tertiary references. An in vitro study of the antimicrobial effects of indigo naturalis prepared from Strobilanthes formosanus Moore. PubMed To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Radiotherapy Combined With Realgar-Indigo Naturalis Formula (RIF) in Kawai S, Iijima H, Shinzaki S, et al. In this manuscript, we reviewed the manufacturing process, chemical composition, traditional applications, pharmacological mechanisms and clinical applications of indigo naturalis, which can provide comprehensive and detailed references to related researchers and contribute to the further development and clinical applications of indigo naturalis. Indole phenol combines with oxygen to form indole phenol free radical in an alkaline environment. Indigo naturalis is a Chinese herbal medicine that has currently been used to treat various inflammatory diseases, including ulcerative colitis. A 20-minute daily walk may improve heart health in those with high CVD risk, Alzheimers: New blood biomarker could predict risk of cognitive decline. Indole alkaloids, especially bisindole nuclear alkaloids, have been widely concerned in the field of anti-infection due to their special structure, strong analogues, high selectivity and low side effects [42]. It also mildly inhibited Aspergillus fumigates and Candida albicans, pathogens associated with nondermatophytic onychomycosis. We include products we think are useful for our readers. At the same time, there are also adverse reactions such as gastrointestinal reactions, liver injury and pulmonary hypertension, but there is no death (Table2). PubMed Patients were randomized to apply 0.5 g of Lindioil ointment containing 10, 50, 100, or 200 mcg/g of indirubin twice daily for 8 weeks, followed by a 12-week safety/extension period. Chen MS, Du LY. Malignant tumor has become one of the major diseases threatening human beings. Short-term and long-term outcomes of indigo naturalis treatment for inflammatory bowel disease. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. Our group's previous studies 1,2 have shown that topical application of indigo naturalis significantly improves psoriatic symptoms. Indigo naturalis is indicated for various kinds of bleeding syndromes, such as hemoptysis and epistaxis, and its powder can be dipped with sterilized cotton and stuffed into the nasal cavity to stop bleeding. BMC Complement Med Ther. Dermatitis is common among indigo dyers, but there is no direct evidence linking this effect to indigo plant or dye exposure.Duke 1985 Adverse events reported in small studies and case reports of indigo naturalis use include phlebitis-induced colitis and reversible pulmonary arterial hypertension, as well as mild liver dysfunction, abdominal pain, and headache.Kim 2018, Matsuno 2018, Nishio 2018 Topical indigo ointment may cause pruritus, rash, erythema, and nasopharyngitis.Cheng 2017, Farahnik 2017, A case report describes the appearance of blue colorectal lesions in the sigmoid colon and rectum in a woman who took a supplement containing qing dai for ulcerative colitis.Kato 2016 Another case report describes the development of pancreatitis in an 11-year-old boy with refractory Crohn disease. With innovation and long-term management, Xian Chinwon Biotech Inc. makes quality indigo naturalis from natural extract through a series of processes to ensure natural purity and safety. In an in vitro study, an ethyl acetate extract of indigo naturalis prepared from S. formosanus Moore inhibited Staphylococcus aureus, Staphylococcus epidermidis, and methicillin-resistant S. aureus. 2018;101:38695. Indirubin in indigo naturalis can inhibit wnt/-Catenin signal transduction by restoring the expression of wif-1, inhibit the expression of TGase1 and down-regulate CDK1 to inhibit the proliferation of keratinocytes [62,63,64]. However, lime is an essential raw material in the process of indigo naturalis manufacture. 2018;96:63645. According to the modern research results, indigo naturalis mainly treats psoriasis by inhibiting the excessive proliferation of keratinocytes, regulating the body immunity, reducing inflammation and anti angiogenes [62,63,64,65, 67]. (Naganuma 2018), In a murine model of oxazolone-induced colitis, indigo naturalis treatment exacerbated mucosal damage associated with colitis despite a reduction in levels of IL-13 (an important cytokine in colitis). The complete remission rate of APL patients with Realgar-indigo naturalis was 96.798%, and the 5-year overall survival rate was 86.88% [54, 55]. 39 Shierqiao Road, Chengdu, 610075, Peoples Republic of China, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, Peoples Republic of China, Zhang Ting,He Ya-nan,Huang Sheng-jie,Deng Xuan&Han Li, Chengdu University of Traditional Chinese Medicine, No. Indirubin is of importance in the antitumor effects of indigo naturalis. In non-melanoma skin cancer, tryptanthrin can inhibit the proliferation of hair follicle cells by inhibiting the activation of ERK1/2 and p38 and reducing the expression of -Catenin [59]. 2011;17:441424. Hospital of Chengdu University of Traditional Chinese Medicine, No. Indigo Naturalis For Psoriasis Treatment | LearnSkin The different effects of indirubin on effector and CD4 + CD25 + regulatory T cells in mice: potential implication for the treatment of autoimmune diseases. 7 8 IN is an extract derived from stems and leaves of several plant species including Baphicacanthus cusia (Nees) Bremek of the Acanthacaea family, with indigo and indirubin considered its main organic ingredients. Indigo naturalis has a variety of pharmacological activities, such as anti-inflammatory, antioxidant, antibacterial, antiviral, immunomodulatory and so on. 2023 BioMed Central Ltd unless otherwise stated. Indirubin inhibits the production of inflammatory cytokines through a variety of signaling pathways, and has a certain dose-dependent [30, 31]. Talbott, W., & Duffy, N. (2015, April 23). CAS We link primary sources including studies, scientific references, and statistics within each article and also list them in the resources section at the bottom of our articles. 2011;129:250211. In the cell viability and induce apoptosis test of 2 human ovarian cancer cell lines, indirubin can inhibit cell activity and induce apoptosis with dose dependence by downregulating the phosphorylation of STAT3 (tyr705), and significantly suppressing the expression of cyclin D1 and c-myc downstream of STAT3 [31]. To improve patient compliance, we have developed a refined formulation in which the blue dye component is removed, leaving only a purple-red color that is closer to . Gastroenterology. A Chinese Herb, Indigo Naturalis, Extracted in Oil (Lindioil) Used Topically to Treat Psoriatic Nails: A Randomized Clinical Trial | Complementary and Alternative Medicine | JAMA Dermatology | JAMA Network Indigo naturalis, a Chinese herb, has been used for decades. The above studies show that indigo naturalis is a potential adjuvant drug for treating APL. 2019;54:8916. 2019;24:4086. Some research suggests that applying a specific product containing indigo naturalis oil extract (Lindioil) to the fingernails and the skin beneath the edge of the nail twice daily for 24 weeks improves psoriasis by . Indigo naturalis Indigo naturalis, also known as qing dai, is a traditional Chinese herbal medicine that people use for treating skin conditions. (Saito 2015), In a randomized, double-blind, placebo-controlled clinical trial in 86 Japanese patients with active ulcerative colitis, the effect of indigo naturalis on clinical response was assessed. Gaitanis G, Magiatis P, Velegraki A, et al. Chin J Chin Mater Med. Liao W, Fu CM, Wang JS, et al. Indigo naturalis and its component tryptanthrin exert anti-angiogenic effect by arresting cell cycle and inhibiting Akt and FAK signaling in human vascular endothelial cells. Am J Chin Med. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Indigo Naturalis for Psoriatic Nails - JAMA Network (Thailand), Indigofera anil L., Indigofera arrecta. Antimicrobial activity of tryptanthrins in Escherichia coli. 2023 Healthline Media UK Ltd, Brighton, UK. From natural dye to herbal medicine: a systematic review of chemical Lin YK, Leu YL, Huang TH, et al. In children with APL, the 5-year event-free survival of RIF group is 100%, as well as intravenous arsenic trioxide after an average follow-up of 3years. Discussion on source,preparation and quality of Indigo Naturalis. Lin YK, Chen HW, Yang SH, et al. Yoshimatsu Y, Naganuma M, Sugimoto S, et al. This ability helps with psoriasis because the condition causes the skin cells to divide too rapidly, which leads to scaly skin and plaques. 2019;148:104409. The anti-TH17 polarization effect of Indigo naturalis and tryptanthrin by differentially inhibiting cytokine expression. Upon rechallenge, the same clinical presentation was noted.Kim 2018 Another case report describes 2 patients with ulcerative colitis who developed wall thickening and edema during administration of the oral powdered form of qing dai. Can diet and exercise reverse prediabetes? Besides, organic composition ratio of indigo naturalis may not be exactly the same, which depended on the source of stems and leaves. Indigo naturalis (IN), which is derived from indigo plants such as Strobilanthes cusia (Nees) Kuntze, Persicaria tinctoria (Aiton) Spach, and Isatis tinctoria L., has been traditionally used in the treatment of hemoptysis, epistaxis, chest pain, aphtha, and infantile convulsion in China for thousands of years. Other studies found that indigo naturalis could repair intestinal mucosa. Using herbal remedies on the skin can cause side effects in some people, such as: When using essential oil, always dilute it with a carrier oil beforehand. [5] The connections are often disrupted in psoriasis. The . It has been shown that indigo naturalis can play an antioxidant role by scavenging oxygen free radicals, improving the activity of superoxide dismutase, inhibiting the production of malondialdehyde, and stabilizing cell membrane permeability [18]. Compared with ATRA therapy, there was no significant difference in blood parameters [8, 75]. Pediatr Dermatol. Deng, S., May, B. H., Zhang, A. L., Lu, C., & Xue, C. C. (2013, October). 2012;139:8936. Ischemic colitis induced by indigo naturalis in a patient with Learn about 11 ways to prevent psoriasis, People who live with psoriasis can choose from a variety of systemic and topical treatments for the condition. Indirubin ameliorates dextran sulfate sodium-induced ulcerative colitis in mice through the inhibition of inflammation and the induction of Foxp3-expressing regulatory T cells. Inhibition of RANTES expression by indirubin in influenza virus-infected human bronchial epithelial cells. Effects: It helps in evading the excess of heat. Patients had been diagnosed with chronic plaque psoriasis for at least 1 year, with less than 20% of body surface area affected by psoriasis. Speak to a doctor before using any new, natural remedy, as some ingredients can interact with existing medications or affect specific medical conditions. Yearly payments, with each season's carbon crop vested over five years (50% in year one, 20% in year two, and 10% in years three to five) Current price offers $30 per credit to farmers. Oncol Lett. There is no cure, but people can manage their symptoms with treatments and natural remedies. Scand J Infect Dis. volume15, Articlenumber:127 (2020) and their antioxidant capacities. Ulcerative colitis using endoscopy. Kim MH, Choi YY, Yang G, et al. Contraindications have not been identified. Chin J Integr Tradit West Med on Digest. In the Tang Dynasty,indigo naturalis is a fashionable cosmetic used for thrush. Gao W, Guo Y, Wang C, et al. Luo C, Xu X, Wei X, et al. . (Bengal, Natal), Indigofera tinctoria (France)., Isatis indigotica Fortune ex Lindl., Isatis tinctoria L. subspecies villarsii, Persicaria tinctoria. This product may be unsafe when used before surgery or other medical procedures. People can also apply topical creams directly to the areas of the skin that psoriasis affects. It has been evaluated for treatment of psoriasis and other dermatological conditions as well as GI diseases such as ulcerative colitis. 2008;105:482631. Zhou W, Zhang XY. 2013;21:3936. They found that compared with single component or dual drug combination, ATI can increase the ubiquitination/degradation of promyelocytic leukemia (PML)-retinoic acid receptor (RAR) oncoprotein, enhance the reprogramming of myeloid differentiation regulators, and enhance G1/G0 block in APL cells by striking multiple targets. These results indicate that indigo naturalis and its some main components have potential as antioxidants. However, excessive or long-term inflammatory response can lead to tissue damage [24]. Article 2020;35:16535. Article (Suzuki 2018), In vitro studies have suggested that the components of indigo naturalis (tryptanthrin, indigo, and indirubin) work synergistically to down-regulate keratinocyte proliferation, improve epidermal differentiation, and reduce oxidative stress and neutrophil inflammation. 2011;19:147. Research on Application of Qingdai (Natural Indigo) in History. 2020;265:113325. These electrophilic groups could promote the release of hydrogen ion from hydroxyl groups and form non free radical superoxide anion, thus stabilizing superoxide anion. Biosci Rep. 2018;38:1. Clinical studies showed that the relapse rate of APL was 12.90% and the total mortality rate was 6.45% by alternately using chemotherapy and realgar-indigo naturalis formula (RIF), mainly consist in realgar and indigo naturalis. (Naganuma 2018), In a randomized, placebo-controlled study in patients with ulcerative colitis, qing dai significantly decreased clinical activity index (CAI) scores over 24 months of administration (P<0.001). It can also inhibit the expression of NF-B regulated genes, including anti apoptotic genes (iap1, iap2, Bcl-2, BCL XL and TRAF1), proliferation genes (cyclin D1 and c-myc), and invasive genes (COX-2 and MMP-9), thus playing anti-inflammatory and anti-tumor activities [30]. A study found that indirubin significantly inhibited TLR4 and NF-B signaling and decreased the level of inflammatory cytokines in mice with lipopolysaccharide (LPS)-induced acute lung injury [25]. Is the ketogenic diet right for autoimmune conditions? At present, indigo naturalis is mostly used as external preparation in treating psoriasis vulgaris and nail psoriasis (Table1). For these bacteria, tryptanthrin has better antibacterial activity than indigo. 2016;1:921. Natural medicines for the treatment of fatigue: Bioactive components, pharmacology, and mechanisms. 2015;407:1695704. IndiGo, India's largest carrier, is all set to potentially close in on a record deal to buy 500 narrow-body A320-family jets from Airbus, according to industrial . 2017;17:439. These include: There is some evidence that vitamin D creams can help with psoriasis. Firstly, the stems and leaves from Baphicacanthus cusia (Nees) Bremek, Polygonum tinctorium Ait or Isatis indigotica Fort are soaked in water until rot. 2019;58:2299304. Clinical efficacy and IL-17 targeting mechanism of Indigo naturalis as a topical agent in moderate psoriasis. Except for promoting intestinal mucosal repairing and ulcer healing, indigo naturalis also can inhibit the gene expression of MMP-1 and TIMP-1 and reduce the damage of colonic mucosa by inhibiting Smads signaling pathway and activating MAPK signal pathway [69, 70]. Exploring the Mechanism of Indigo Naturalis in the Treatment of Upon discontinuation, the patient's signs and symptoms resolved. 2012;380:160619. (Kawai 2017), In a murine model of ulcerative colitis, indigo naturalis significantly reduced Disease Activity Index scores and histopathologic scores compared with the model (control) group (P<0.05 and P<0.01, respectively). It is also known as Oregon grape. J Dermatol Sci. There are many methods of using Aloe vera, which people can find in many different products. It was found that there were obvious differences in nucleoside content of indigo naturalis from different producing areas or batches. Yu ST, Chen TM, Tseng SY, et al. Strobilanthes cusia (Nees) Kuntze, a multifunctional traditional Chinese medicinal plant, and its herbal medicines: A comprehensive review. Kim SA, Kim YC, Kim SW, et al. 2016;14:794800. Additionally, researches of indigo naturalis mainly focused on indigo, indirubin and tryptophan, but less on other components. Han Li or Xie Chun-guang. Development of an Indigo Naturalis Suppository for Topical Induction Therapy in Patients with Ulcerative Colitis. Hutchinson EC. We searched PubMed, web of science, CNKI, Google academic, Elsevier and other databases with the key words of Indigo naturalis, and reviewed and sorted out the modern research of indigo naturalis based on our research results. 2020;142:14856. Teng J. Textual research on indigo naturalis and the medicinal blue herbs. One case report describes development of pancreatitis with use of oral indigo naturalis; another describes colitis and pulmonary hypertension with a supplement containing qing dai. Article This method can accurately and rapidly determine the content of heavy metals mentioned above. A 2013 systematic review found evidence to suggest that using vitamin D creams could be as effective as corticosteroid treatments for treating symptoms. Ozawa K, Mori D, Hatanaka A, et al. Meanwhile, it is necessary to monitor adverse reactions of indigo naturalis for a long-time use. Pain is a common symptom of psoriasis, which means, in theory, reflexology may be helpful for psoriasis pain. (Wang 2018), In patients with mild to severe atopic dermatitis, topical application of indigo naturalis ointment for 6 weeks resulted in a significant improvement in area severity scores compared to vehicle controls (49.9% vs 19.6% reduction from baseline, respectively; P=0.0235). Indigo is mostly used as a source of dye. Treatment of psoriatic nails with indigo naturalis oil extract: a non-controlled pilot study. CAS Additionally, indigo naturalis can also play an anti-inflammatory role by inhibiting intracellular Ca2+ concentration. The main active components and targets of IN were . 2018;23:2743. You should talk with your health care provider for complete information about the risks and benefits of using this product. Frontiers | A Comprehensive Review of the Chemistry, Pharmacokinetics Indigo naturalis and its some active ingredients have been proved to have significant anti-inflammatory effects, whose mechanism isthe down-regulation of some inflammation factors and the inhibition of NO production [25, 26]. Lai JL, Liu YH, Peng YC, et al. Biochem Cell Biol. It has very good clinical effect on psoriasis, leukemia and ulcerative colitis. Terms and Conditions, detected the effect of indirubin on ATP-induced macrophage immune response: neutral red dye uptake was used to measure cell death, and the ROS level was tested by dihydroethidium fluorescence probe. Chinese Medicine Patients were instructed to apply 1 to 2 drops of Lindioil to one hand and 1 to 2 drops of calcipotriol to the other hand twice daily for 24 weeks. Urushikubo J, Yanai S, Nakamura S, et al. Interestingly, in the presence of light, a lower dose of indigo (MIC/2) can show antibacterial effects [40]. Eisenbrand G, Hippe F, Jakobs S, et al. Additionally, more patients preferred Lindioil (82.1%) to treat their psoriasis compared to calcipotriol (17.9%). Learn more. Indirubin inhibits ATP-induced phagocytosis attenuation, ROS production and cell death of macrophages. IHG Hotels & Resorts brings lifestyle brand Hotel Indigo to the 1188 Liutai Avenue, Chengdu, 611137, China, You can also search for this author in 1995;1:268. Indigo dye, Southern Banlangen, and Indigo Naturalis are its most important usages. Int Arch Allergy Immunol. https://www.iucnredlist.org/species/176545/7263416. The potential role of Th17 cells and Th17-related cytokines in the pathogenesis of lupus nephritis. CAS A study has shown that indigo naturalis can inhibit oxazolidone induced allergic dermatitis by reducing eosinophil recruitment and production of Th2 related cytokines. Health stores and online stores sell Mahonia aquifolium essential oils, tinctures, and creams. 2017;40:112. The anti-angiogenic effect of tryptanthrin is mediated by the inhibition of apelin promoter activity and shortened mRNA half-life in human vascular endothelial cells. However, patient compliance is hindered because the preparation is unsightly and stains clothing. Hotel Indigo, part of IHG Hotels & Resorts' Luxury & Lifestyle Collection, hits a triple milestone with the opening of Hotel Indigo Galapagos on the island of San Cristobal. Indigo Naturalis for Ulcerative Colitis - Journal of Plant Medicines 2018;32:568. Chin J Hemat. Any medical information published on this website is not intended as a substitute for informed medical advice and you should not take any action before consulting with a healthcare professional. Indirubin can also improve the proliferation of keratinocytes, inhibit the activation of JAK3/STAT3 pathway, reduce the osmosis of CD3+T cells, T cells and CD11b+neutrophils, and decrease the level of T cells in spleen and lymph nodes [49]. People can use certain treatments, home remedies, and lifestyle changes to prevent psoriasis flare-ups. "Indigo" can refer to several species of Indigofera (eg, I. anil L, I. suffruticosa Mill.) They also had lower levels of interleukin-17 (IL-17), which is a marker of inflammation in people with psoriasis. Pharmacol Res. Adachi S, Hoshi N, Inoue J, et al. The inorganic ingredients of indigo naturalis was consist of 70% calcium carbonate, 10% silica dioxide and calcium hydroxide [3, 11]. Carbon by Indigo | Successful Farming Its beneficial action is believed to result from an antiproliferative effect on keratinocytes and repair of the epidermal barrier. Biochem Biophys Res Commun. Article By using this website, you agree to our The reaction mechanism of indigo and indirubin. This herb has a history of use in treating inflammatory conditions, including psoriasis. Phase clinical trial of compound Huangdai tablets in newly diagnosed acute promyelocytic leukemia. No evidence-based recommendations were made. If you buy through links on this page, we may earn a small commission Heres our process. Modern researches found that indigo naturalis has anti-inflammatory, antioxidant, antibacterial, immune regulation and other activities [4,5,6]. Oncotarget. Cell Prolif. This information relates to an herbal, vitamin, mineral or other dietary supplement. The good news is using indigo powder for your hair can prevent hair fall. "Stasiak 2014 Before the development of synthetic aniline and indigo dyes, indigo plants were grown commercially in the East Indies, South America, and Central America. PHOTO: REUTERS. In fact, the process of soaking and adding lime is not only the conversion of indole phenol, as well as the transformation of other substances.
