Anthraquinone laxatives use and colorectal cancer: A systematic review and meta‐analysis of observational studies

Lombardi, Niccolò; Crescioli, Giada; Maggini, Valentina; Bellezza, Raffaele; Landi, Iacopo; Bettiol, Alessandra; Menniti‐Ippolito, Francesca; Ippoliti, Ilaria; Mazzanti, Gabriela; Vitalone, Annabella; Gallo, Eugenia; Sivelli, Francesco; Sofi, Francesco; Gensini, Gian Franco; Vannacci, Alfredo; Firenzuoli, Fabio

doi:10.1002/ptr.7373

Cited by 9 publications

(5 citation statements)

References 27 publications

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“…50 In line with our current study, a recent systematic review on the use of anthraquinone laxatives reported that it is not possible to conclude on the association of anthraquinone laxatives with CRC due to the lack of robust studies; thus, there is a need for high-quality studies to formally test the association of increased risk of CRC with use of stimulant laxatives. 95 …”

Section: Discussionmentioning

confidence: 99%

Review article: do stimulant laxatives damage the gut? A critical analysis of current knowledge

Whorwell,

Lange,

Scarpignato

2024

Therap Adv Gastroenterol

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Stimulant laxatives are well established as first- or second-line treatments for constipation and although they have a reliable therapeutic effect, alleged safety concerns still exist, particularly with long-term use. The potential harmful effects on the gastrointestinal system (including carcinogenicity) of the long-term use of diphenylmethane [bisacodyl, sodium picosulfate (SPS)] and senna stimulant laxatives were assessed in a comprehensive review of the publications identified in literature searches performed in PubMed and Embase up to and including June 2023. We identified and reviewed 43 publications of interest. While stimulant laxatives at supratherapeutic doses have been shown to cause structural alterations to surface absorptive cells in animals and humans, these effects are reversible and not considered clinically relevant. No formal long-term studies have demonstrated morphological changes in enteric neural elements or intestinal smooth muscle with bisacodyl or SPS in humans. Furthermore, there is no convincing evidence that stimulant laxatives are associated with the development of colon cancer, and in fact, chronic constipation itself has been reported to potentially increase the risk of colon cancer, therefore, the use of stimulant laxatives might reduce this risk. Many studies suggesting a possible harmful effect from laxatives were limited by their failure to consider confounding factors such as concomitant neurological disease, metabolic disorders, and age. These findings highlight the lack of evidence for the harmful effects of laxatives on the colon, and thus, the benefits of treatment with stimulant laxatives, even in the long-term, should be reconsidered for the management of patients with constipation.

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Section: Discussionmentioning

confidence: 99%

Review article: do stimulant laxatives damage the gut? A critical analysis of current knowledge

Whorwell,

Lange,

Scarpignato

2024

Therap Adv Gastroenterol

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“…A retrospective study including 718 MC patients and 2,154 healthy people showed that MC is not related to increased diagnosis of colorectal cancer but enhanced polyp detection due to “chromo-endoscopy-like effect” ( Abu Baker et al, 2018 ). A systemic review aiming to determine the effects of anthraquinone laxatives on colorectal cancer has concluded that a history of anthraquinone laxatives use brought an increased trend in colorectal cancer development, although not showing any significance ( Lombardi et al, 2020 ; Lombardi et al, 2022 ). Therefore, medications or therapeutic interventions for MC are required.…”

Section: Melanosis Colimentioning

confidence: 99%

Review on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coli

et al. 2023

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Backgrounds: The incidence of melanosis coli (MC) has gradually increased annually, attracting significant attention and efforts into this field. A potential risk for MC is the long-term use of anthraquinone laxatives in patients with constipation. Most traditional cathartic drugs are made from herbs containing anthraquinone compounds. This review aims to provide guidance for the application of traditional Chinese herbs containing anthraquinones for physicians and researchers.Materials and methods: We reviewed risk factors and pathogenesis of MC, and natural anthraquinones isolated from TCM herbs. We searched Pubmed and CNKI databases for literature related to MC with keywords such as“traditional Chinese medicine”, “Chinese herbs”, “anthraquinones”, and “melanosis coli”. The literature is current to January 2023 when the searches were last completed. After the literature retrieval, the TCM herbs containing anthraquinones (including component identification and anthraquinone content determination) applied in clinical were selected. According to the collected evidence, we provide a list of herbs containing anthraquinones that could cause MC.Results: We identified 20 herbs belonging to 7 families represented by Polygonaceae, Fabaceae, Rhamnaceae, and Rubiaceae, which may play a role in the pathogenesis of MC. Among these, the herbs most commonly used include Dahuang (Rhei Radix et Rhizome), Heshouwu (Radix Polygoni Multiflori), Huzhang (Rhizoma Polygoni Cuspidati), Juemingzi (Semen Cassiae), Luhui (Aloe) and Qiancao (Rubiae Radix et Rhizoma).Conclusion: Due to a lack of awareness of the chemical composition of TCM herbs, many patients with constipation and even some TCM physicians take cathartic herbal remedies containing abundant anthraquinones to relieve defecation disturbances, resulting in long-term dependence on these herbs, which is potentially associated with most cases of MC. When such treatments are prescribed, TCM physicians should avoid long-term use in large doses to reduce their harm on colonic health. Individuals who take healthcare products containing these herbs should also be under the supervision of a doctor.

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“…These official rhubarbs contain anthraquinones, notably aloe-emodin, rhein, emodin, chrysophanol, and physcion. Anthraquinones are recognized as the most crucial chemical components in the official rhubarbs with several bioactivities such as laxative ( Lombardi et al, 2022 ), anti-inflammation ( Zhang et al, 2020 ), anti-bacterial ( Friedman et al, 2020 ), anti-diabetic ( Arvindekar et al, 2015 ), and anti-cancer properties ( Adnan et al, 2021 ). Most anthraquinones in TCM or herbs exist in the form of glycosides ( Zhao et al, 2014 ; Jintao et al, 2018 ) and plant parts like senna leaves ( Vilanova-Sanchez et al, 2018 ), and Aloe vera ( Hong et al, 2018 ); such plant parts are used to treat constipation ( de Witte, 1993 ).…”

Section: Introductionmentioning

confidence: 99%

Qualitative and quantitative analysis methods for quality control of rhubarb in Taiwan’s markets

Au,

Ho,

Chang

2024

Front. Pharmacol.

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Introduction: Rhubarb is a traditional Chinese medicine (TCM) used to release heat and has cathartic effects. Official rhubarb in Taiwan Herbal Pharmacopeias 4th edition (THP 4th) and China Pharmacopeia 2020 (CP 2020) are the roots and rhizomes of Rheum palmatum L., Rheum tanguticum Maxim. ex Balf., and Rheum officinale Baill. However, the Rheum genus is a large genus with many different species, and owing to the similarity in appearance and taste with official rhubarb, there needs to be more clarity in the distinction between the species of rhubarb and their applications. Given the time-consuming and complicated extraction and chromatography methods outlined in pharmacopeias, we improved the qualitative analysis and quantitative analysis methods for rhubarb in the market. Hence, we applied our method to identify the species and quality of official and unofficial rhubarb.Method: We analyzed 21 rhubarb samples from the Taiwanese market using a proposed HPLC-based extraction and qualitative analysis employing eight markers: aloe-emodin, rhein, emodin, chrysophanol, physcion, rhapontigenin, rhaponticin, and resveratrol. Additionally, we developed a TLC method for the analysis of rhubarb. KEGG pathway analysis was used to clarify the phytochemical and pharmacological knowledge of official and unofficial rhubarb.Results: Rhein and rhapontigenin emerged as key markers to differentiate official and unofficial rhubarb. Rhapontigenin is abundant in unofficial rhubarb; however, rhein content was low. In contrast, their contents in official rhubarb were opposite to their contents in unofficial rhubarb. The TLC analysis used rhein and rhapontigenin to identify rhubarb in Taiwan’s markets, whereas the KEGG pathway analysis revealed that anthraquinones and stilbenes affected different pathways.Discussion: Eight reference standards were used in this study to propose a quality control method for rhubarb in Taiwanese markets. We propose a rapid extraction method and quantitative analysis of rhubarb to differentiate between official and unofficial rhubarb.

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Anthraquinone laxatives use and colorectal cancer: A systematic review and meta‐analysis of observational studies

Cited by 9 publications

References 27 publications

Review article: do stimulant laxatives damage the gut? A critical analysis of current knowledge

Review article: do stimulant laxatives damage the gut? A critical analysis of current knowledge

Review on melanosis coli and anthraquinone-containing traditional Chinese herbs that cause melanosis coli

Qualitative and quantitative analysis methods for quality control of rhubarb in Taiwan’s markets

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