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Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments.
J Ethnopharmacol. 2020 Oct 28; 261:113133.JE

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders.

AIM OF THE STUDY

To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ.

MATERIAL AND METHODS

Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-β-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg2+), calcium (Ca2+), phosphorus (P), were estimated. Blood glycosylated hemoglobin (HbA1C) were also estimated. kidney and liver were used for biochemical estimation of oxidative stress markers such as lipid peroxidation, superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity. The kidney and pancreas were used for histopathological study. Further, HPLC chemoprofiling of CM extract and in-silico molecular simulation experiments were performed.

RESULTS

At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 μg/mg of extract) and quercitrin (19.07 μg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein.

CONCLUSIONS

Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum.

Authors+Show Affiliations

University of Lomé, Togo; University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania; Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. Electronic address: mabozou@gmail.com.University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania.University of Lomé, Togo.University of Lomé, Togo.University of Lomé, Togo.University of Ouagadougou UFR/SVT, 09 BP 848, Ouagadougou 09, Burkina Faso.University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania.Department of Biotechnology, Siddaganga Institute of Technology, Tumkur, 572103, Karnataka, India.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India.University of Medicine and Pharmacy "Iuliu Hateganu", Emil Isaac Street 13, 400023, Cluj-Napoca, Romania.University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania.University of Lomé, Togo.University of Agricultural Science and Veterinary Medicine, Manastur Street. 3-5, 400372, Cluj-Napoca, Romania.Sree Siddaganga College of Pharmacy, B.H. Road, Tumkur, 572 102, Karnataka, India. Electronic address: veeresh36@gmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32673708

Citation

Kpemissi, Mabozou, et al. "Nephroprotective Effect of Combretum Micranthum G. Don in Nicotinamide-streptozotocin Induced Diabetic Nephropathy in Rats: In-vivo and In-silico Experiments." Journal of Ethnopharmacology, vol. 261, 2020, p. 113133.
Kpemissi M, Potârniche AV, Lawson-Evi P, et al. Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments. J Ethnopharmacol. 2020;261:113133.
Kpemissi, M., Potârniche, A. V., Lawson-Evi, P., Metowogo, K., Melila, M., Dramane, P., Taulescu, M., Chandramohan, V., Suhas, D. S., Puneeth, T. A., S, V. K., Vlase, L., Andrei, S., Eklu-Gadegbeku, K., Sevastre, B., & Veerapur, V. P. (2020). Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments. Journal of Ethnopharmacology, 261, 113133. https://doi.org/10.1016/j.jep.2020.113133
Kpemissi M, et al. Nephroprotective Effect of Combretum Micranthum G. Don in Nicotinamide-streptozotocin Induced Diabetic Nephropathy in Rats: In-vivo and In-silico Experiments. J Ethnopharmacol. 2020 Oct 28;261:113133. PubMed PMID: 32673708.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nephroprotective effect of Combretum micranthum G. Don in nicotinamide-streptozotocin induced diabetic nephropathy in rats: In-vivo and in-silico experiments. AU - Kpemissi,Mabozou, AU - Potârniche,Adrian-Valentin, AU - Lawson-Evi,Povi, AU - Metowogo,Kossi, AU - Melila,Mamatchi, AU - Dramane,Pare, AU - Taulescu,Marian, AU - Chandramohan,Vivek, AU - Suhas,Doddamavattur Shivalingaiah, AU - Puneeth,Tumbadi Adinarayanashetty, AU - S,Vijaya Kumar, AU - Vlase,Laurian, AU - Andrei,Sanda, AU - Eklu-Gadegbeku,Kwashie, AU - Sevastre,Bogdan, AU - Veerapur,Veeresh Prabhakar, Y1 - 2020/07/14/ PY - 2020/01/17/received PY - 2020/06/01/revised PY - 2020/06/22/accepted PY - 2020/7/17/pubmed PY - 2021/2/25/medline PY - 2020/7/17/entrez KW - Combretum micranthum KW - Diabetic nephropathy KW - Molecular docking KW - Molecular dynamic KW - PPARα KW - PPARγ SP - 113133 EP - 113133 JF - Journal of ethnopharmacology JO - J Ethnopharmacol VL - 261 N2 - ETHNOPHARMACOLOGICAL RELEVANCE: Combretum micranthum G. Don (CM) is extensively used in traditional medicine throughout West Africa and commonly known as "long-life herbal tea" or "plant to heal". Further, traditional healers frequently use the title plant to mitigate of renal disorders. AIM OF THE STUDY: To explore the nephroprotective property of standardised hydroalcoholic extract of Combretum micranthum in nicotinamide-streptozotocin induced diabetic nephropathy in rats. In addition, in-silico computational experiments were performed with bioactive compounds of the title plant against PPARα and PPARγ. MATERIAL AND METHODS: Male rats were made diabetic by a single intraperitoneal (ip) injection of STZ (50 mg/kg), 15 min after ip administration of NA (100 mg/kg) dissolved in normal saline. The diabetic rats received CM extract (200 and 400 mg/kg p.o.) daily, for eight weeks. Body weights and blood glucose (non-fasting and fasting) of rats were measured weekly. Daily food and water consumption were also measured. After 8 weeks of treatment, urine biochemical parameters such as N-Acetyl-β-D-Glucosaminidase (NAG), urea (UR), uric acid (UA), creatinine (CRE), and serum markers of diabetes, kidney damage and liver damage such as insulin, lipid parameters), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transferase (γGT), albumin (Alb), magnesium (Mg2+), calcium (Ca2+), phosphorus (P), were estimated. Blood glycosylated hemoglobin (HbA1C) were also estimated. kidney and liver were used for biochemical estimation of oxidative stress markers such as lipid peroxidation, superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity. The kidney and pancreas were used for histopathological study. Further, HPLC chemoprofiling of CM extract and in-silico molecular simulation experiments were performed. RESULTS: At the end of eight weeks, renal damage induced by the consequence of prolong diabetic condition was confirmed by altered levels of serum and urine kidney and liver function markers, oxidative stress markers and histopathological variations in kidney. Treatment with CM extract ameliorated the diabetes mellitus-induced renal biochemical parameters and histopathological changes. Further, HPLC-UV & MS experiments revealed that CM extract contains several bioactive compounds including hyperozide (62.35 μg/mg of extract) and quercitrin (19.07 μg/mg of extract). In-silico experiment exhibited cianidanol (-17.133), epicatechin (-15.107) exhibited higher docking score against PPARα and luteoforol (-11.038), epigallocatechin (-10.736) against PPARγ. Based on docking and drug likeness score, four bioactive compounds were selected for molecular dynamic experiments. Cianidanol and epigallocatechin out of the 30 compounds are concluded as a potential candidate for the treatment of DN through activating PPARα and PPARγ target protein. CONCLUSIONS: Taken together, the present study provided the scientific footage for the traditional use of Combretum micranthum. SN - 1872-7573 UR - https://www.unboundmedicine.com/medline/citation/32673708/Nephroprotective_effect_of_Combretum_micranthum_G__Don_in_nicotinamide_streptozotocin_induced_diabetic_nephropathy_in_rats:_In_vivo_and_in_silico_experiments_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-8741(20)33014-2 DB - PRIME DP - Unbound Medicine ER -