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      Acute and Subchronic Toxicological Study of the Cocktail Extract from Curcuma xanthorrhiza Roxb, Phyllanthus niruri L. and Morinda citrifolia L.

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          Abstract

          Curcuma xanthorrhiza Roxb , Phyllanthus niruri L., and Morinda citrifolia L. are Indonesian medicinal herbs used empirically as traditional therapeutics for maintaining health. The cocktail extract of these three plants (CECPM) had been developed and demonstrated immunostimulant activity in rats. This study aimed to evaluate the acute and subchronic toxicity of CECPM in vivo. The acute toxicity assay was conducted by orally administering a range dose of CECPM (313, 625, 1250, 2500, or 5000 mg/kg body weight (bw) on female mice once and then evaluating the toxic symptom every day for 14 days later. The chronic toxicity test was carried out by giving various doses of CECPM (600, 800, and 1000 mg/kg·bw) to female and male rats orally continuously for 90 consecutive days. The signs of toxicities were evaluated at the 90- and 28 days postadministration. The acute oral toxicity assays showed that there was no toxic syndrome and mortality found during the period of the experiment. The lethal dose level (LD 50) of CECPM was more than 5000 g/kg, which was categorized as practically non-toxic. Meanwhile, in the sub-chronic toxicity study, some parameters tested at 90 days postadministration and after 28 days of withdrawal, such as the body weight, relative organ weight, food intake, hematological and biochemical blood parameters, and also histopathological examination of five primary tissues (heart, liver, kidney, spleen, and lung) revealed no abnormalities. There was no-observed adverse effect level (NOAEL) for the present study of CECPM 1000 mg/kg·bw of the rat. Therefore, it is concluded that the orally administered CECPM was relatively nontoxic during acute and subchronic toxicology studies.

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          Synergistic Effects of Chinese Herbal Medicine: A Comprehensive Review of Methodology and Current Research

          Traditional Chinese medicine (TCM) is an important part of primary health care in Asian countries that has utilized complex herbal formulations (consisting 2 or more medicinal herbs) for treating diseases over thousands of years. There seems to be a general assumption that the synergistic therapeutic effects of Chinese herbal medicine (CHM) derive from the complex interactions between the multiple bioactive components within the herbs and/or herbal formulations. However, evidence to support these synergistic effects remains weak and controversial due to several reasons, including the very complex nature of CHM, misconceptions about synergy and methodological challenges to study design. In this review, we clarify the definition of synergy, identify common errors in synergy research and describe current methodological approaches to test for synergistic interaction. We discuss the strengths and weaknesses of these models in the context of CHM and summarize the current status of synergy research in CHM. Despite the availability of some scientific data to support the synergistic effects of multi-herbal and/or herb-drug combinations, the level of evidence remains low, and the clinical relevancy of most of these findings is undetermined. There remain significant challenges in the development of suitable methods for synergistic studies of complex herbal combinations.
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            A study on the fate of curcumin in the rat.

            The uptake, distribution and excretion of curcumin in Sprague-Dawley rats has been studied. When administered orally in a dose of 1 g/kg, curcumin was excreted in the faeces to about 75%, while negligible amounts of curcumin appeared in the urine. Measurements of blood plasma levels and biliary excretion showed that curcumin was poorly absorbed from the gut. No apparent toxic effects were seen after doses of up to 5 g/kg. When intravenously injected or when added to the perfusate of the isolated liver, curcumin was actively transported into bile, against concentration gradients of several hundred times. The major part of the drug was however metabolized. In suspensions of isolated hepatocytes or liver microsomes 90% of the added curcumin was metabolized within 30 min. In view of the poor absorption, rapid metabolism and excretion of curcumin, it is unlikely that substantial concentrations of curcumin occur in the body after ingestion.
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              Antioxidant activities of curcumin, demethoxycurcumin and bisdemethoxycurcumin

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                Author and article information

                Contributors
                Journal
                J Toxicol
                J Toxicol
                jt
                Journal of Toxicology
                Hindawi
                1687-8191
                1687-8205
                2024
                27 March 2024
                : 2024
                : 9445226
                Affiliations
                1Research Center for Pharmaceutical Ingredients and Traditional Medicine, National Research and Innovation Agency (BRIN), Bogor, Indonesia
                2Research Center for Agroindustry, National Research and Innovation Agency (BRIN), Bogor, Indonesia
                3Research Center for Sustainable Production System and Life Cycle Assessment, National Research and Innovation Agency (BRIN), Tangerang Selatan, Indonesia
                4Research Center for Vaccine and Drugs, National Research and Innovation Agency (BRIN), Bogor, Indonesia
                5Directorate of Utilization of Research and Innovation by Industry, National Research and Innovation Agency (BRIN), Jakarta, Indonesia
                Author notes

                Academic Editor: Zongming Ren

                Author information
                https://orcid.org/0000-0002-0562-5785
                https://orcid.org/0000-0003-0994-8677
                https://orcid.org/0000-0002-6139-7625
                https://orcid.org/0009-0000-2776-1342
                https://orcid.org/0009-0009-7325-5198
                https://orcid.org/0000-0002-6270-3356
                https://orcid.org/0000-0001-9145-2093
                https://orcid.org/0000-0002-9271-4304
                https://orcid.org/0000-0002-5388-6285
                https://orcid.org/0009-0002-7179-5499
                Article
                10.1155/2024/9445226
                10990647
                38571743
                49a06f61-ab2f-4f04-bd5f-048078eb2ca8
                Copyright © 2024 Idah Rosidah et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 August 2023
                : 27 February 2024
                : 7 March 2024
                Funding
                Funded by: Center for Pharmaceuticals and Medical of Technology
                Funded by: The Assessment and Application of Technology Research Organization-BPPT
                Funded by: Research and Innovation Program Indonesia (RIIM)
                Funded by: Badan Riset dan Inovasi Nasional
                Categories
                Research Article

                Toxicology
                Toxicology

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