Cadmium, a nephrotoxic heavy metal, poses significant health risks that may be mitigated by the phytocompounds in ethnobotanicals like Aframomum melegueta and Rauvolfia vomitoria.
Objective
To evaluate the modulatory potential of Aframomum melegueta and Rauvolfia vomitoria on myeloperoxidase (MPO) and nuclear factor kappa B (NF-Κβ) expression, alongside histomorphological changes in cadmium chloride (CdCl2)-induced renal toxicity.
Methods
Twenty-five adult Wistar rats (200 g) were divided into five groups (n = 7). Group I was the control, while Groups II–V received CdCl2 (30 mg/kg BW, weekly). Group II received no treatment; Groups III and IV were administered Aframomum melegueta and Rauvolfia vomitoria extract (200 mg/kg BW daily), respectively. Group V received both extracts (200 mg/kg BW daily). After 28 days, kidneys were excised for histological and mRNA expression of myeloperoxidase and NF-κB. Data were analysed using one-way ANOVA, with p ≤ 0.05 considered significant.
Results
Aframomum melegueta and Rauvolfia vomitoria extracts significantly repressed MPO and NF-κB expression, with co-treatment exhibiting a stronger downregulatory effect (p < 0.05). Histological analysis also showed improved renal architecture, as treatments mitigated histoarchitectural abnormalities observed in the cadmium-exposed untreated rats.
Conclusion
Findings suggest the potential therapeutic effects of Aframomum melegueta and Rauvolfia vomitoria in mitigating cadmium-induced kidney toxicity.
SatarugS. Dietary cadmium intake and its effects on kidneys. Toxics2018; 6(1): 1–23.
8.
SaintilnordWNTenlepSYNPrestonJD, et al.Chronic exposure to cadmium induces differential methylation in mice spermatozoa. Toxicol Sci2021; 180(2): 262–276.
9.
RenuKChakrabortyRMyakalaH, et al.Molecular mechanism of heavy metals (lead, chromium, arsenic, mercury, nickel and cadmium) - induced hepatotoxicity – a review. Chemosphere2021; 271: 129735.
10.
GengHXWangL. Cadmium: toxic effects on placental and embryonic development. Environ Toxicol Pharmacol2019; 67: 102–107.
11.
AmamouFNemmicheSMezianeRK, et al.Protective effect of olive oil and colocynth oil against cadmium-induced oxidative stress in the liver of Wistar rats. Food Chem Toxicol2015; 78: 177–184.
12.
MatovićVBuhaADukić-ĆosićD, et al.Insight into the oxidative stress induced by lead and/or cadmium in blood, liver and kidneys. Food Chem Toxicol2015; 78: 130–140.
13.
IjazMUShahzadiSHamzaA, et al.Alleviative effects of pinostrobin against cadmium-induced renal toxicity in rats by reducing oxidative stress, apoptosis, inflammation, and mitochondrial dysfunction. Front Nutr2023; 10: 1175008.
14.
RaniAKumarALalA, et al.Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res2014; 24(4): 378–399.
15.
QingYYangJZhuY, et al.Dose–response evaluation of urinary cadmium and kidney injury biomarkers in Chinese residents and dietary limit standards. Environ Health2021; 20(1): 1–9.
16.
AdebayoAAAdemosunAOObohG. Chemical composition, antioxidant, and enzyme inhibitory properties of Rauwolfia vomitoria extract. J Compl Integr Med2023; 20(3): 597–603.
17.
EkongMBPeterAIEdaghaIA, et al.Rauwolfia vomitoria inhibits olfaction and modifies olfactory bulb cells. Brain Res Bull2016; 124: 206–213.
18.
YuJChenQ. Antitumor activities of Rauwolfia vomitoria extract and potentiation of gemcitabine effects against pancreatic cancer. Integr Cancer Ther2014; 13(3): 217–225.
19.
EkongMBPeterAIEkpeneUU. Co-administration of Rauwolfia vomitoria with Gongronema latifolium or Vernonia amygdalina on spatial learning, memory, and some bio-molecules. Asian J Med Sci2015; 7(1): 82–87.
20.
Ebuehi OsaretinATIroghamaAIgwo-Ezikpe MiriamN, et al.Comparative toxicity studies of Rauwolfia vomitoria leaf and root extracts in Wistar rats. Int J Biol Med Res2018; 9(2): 6357–6362. https://www.biomedscidirect.com/
21.
AkinwumiKAAkinwumiKAOlabodeOO, et al.The protective effect of methanol extract of Rauvolfia vomitoria against the clastogenicity and hepatotoxicity of sodium arsenite in mice. J Cancer Res Updates2018; 7(4): 109–118.
22.
AaghazSSharmaKJainR, et al.β-Carbolines as potential anticancer agents. Eur J Med Chem2021; 216: 113321.
23.
FangTXueZSLiJ, et al.Rauwolfia vomitoria extract suppresses benign prostatic hyperplasia by reducing expression of androgen receptor and 5α-reductase in a rat model. J Integr Med2021; 19(3): 258–264.
24.
SuzukiKNomuraINinomiyaM, et al.Synthesis and antimicrobial activity of β-carboline derivatives with N 2 -alkyl modifications. Bioorg Med Chem Lett2018; 28(17): 2976–2978.
25.
DelimontNMHaubMDLindshieldBL. The impact of tannin consumption on iron bioavailability and status: a narrative review Corresponding Author: Brian L Lindshield Additional Authors: Nicole M Delimont. Mark D Haub Am Soc Nutr2017; 3: 1–36.
26.
XieZCaoNWangC. A review on β-carboline alkaloids and their distribution in foodstuffs: a class of potential functional components or not?Food Chem2021; 348: 129067.
27.
TimilsenaYPPhosanamAStockmannR. Perspectives on saponins: food functionality and applications. Int J Mol Sci2023; 24(17): 13538.
28.
AdefeghaSAObohGOkekeBM, et al.Comparative effects of alkaloid extracts from Aframomum melegueta (Alligator pepper) and Aframomum danielli (Bastered melegueta) on enzymes relevant to erectile dysfunction. J Diet Suppl2017; 14(5): 542–552.
29.
OnojaSOOmehYNEzejaMI, et al.Evaluation of the in vitro and in vivo antioxidant potentials of Aframomum melegueta methanolic seed extract. J Trop Med2014; 2014: 159343.
30.
AbdouRMEl-MaadawyWHHassanM, et al.Nephroprotective activity of Aframomum melegueta seeds extract against diclofenac-induced acute kidney injury: a mechanistic study. J Ethnopharmacol2021; 273: 113939.
31.
AmadiSWZhangYWuG. Research progress in phytochemistry and biology of Aframomum species. Pharm Biol2016; 54(11): 2761–2770.
32.
DurazzoALucariniMSoutoEB, et al.Polyphenols: a concise overview on the chemistry, occurrence, and human health. Phyther Res2019; 33(9): 2221–2243.
33.
CörDKnezŽHrnčičMK. Antitumour, antimicrobial, antioxidant and antiacetylcholinesterase effect of Ganoderma Lucidum terpenoids and polysaccharides: a review. Molecules2018; 23(3): 1–21.
ChenH-HHuangY-LWuC-Y, et al.Plasma myeloperoxidase interactions with cadmium, lead, arsenic, and selenium and their impact on chronic kidney disease. Ecotoxicol Environ Saf2025; 290: 117726.
36.
MitchellJPCarmodyRJ. NF-κB and the transcriptional control of inflammation. Int Rev Cell Mol Biol2018; 335: 41–84.
37.
LiuTZhangLJooD, et al.NF-κB signaling in inflammation. Signal Transduct Targeted Ther2017; 2: 17023.
38.
SchindhelmRKVan Der ZwanLPTeerlinkT, et al.Myeloperoxidase: a useful biomarker for cardiovascular disease risk stratification?Clin Chem2009; 55(8): 1462–1470.
39.
LinWChenHChenX, et al.The roles of neutrophil-derived Myeloperoxidase (MPO) in diseases: the new progress. Antioxidants2024; 13(1): 132.
40.
AkinpeluMAdeniyiTAbiodunO, et al.Cymbopogon citratus: a modulator of Tnf-α and IL-10 in NSAID-induced hepatorenal toxicity in adult Wistar rats. Bull Pharm Sci Assiut Univ2024; 47(2): 1251–1262.
41.
AdeniyiTAkinpeluMOloyeJ, et al.Attenuation of cadmium toxicity by methanol extracts of Rauvolfia vomitoria and Aframomum melegueta leaves. Folia Medica Indones2024; 60(2): 94–102.
42.
ParkYSJungSTKangSG, et al.Antioxidants and proteins in ethylene-treated kiwifruits. Food Chem2008; 107(2): 640–648.
43.
PatelRKPatelJBTrivediPD. Spectrophotometric method for the estimation of total alkaloids in the Tinospora cordifolia M. and its herbal formulations. Int J Pharm Pharmaceut Sci2015; 7(10): 249–251.
44.
MazzaraETorresiJFicoG, et al.A comprehensive phytochemical analysis of terpenes, Polyphenols and cannabinoids, and micromorphological characterization of 9 commercial varieties of Cannabis sativa L. Plants2022; 11: 891.
45.
Le AVParks SENguyen MH, et al.Improving the vanillin-sulphuric acid method for quantifying total saponins. Technologies2018; 6(3): 1–12.
46.
Araujo-LeónJACantillo-CiauZRuiz-CiauDV, et al.HPLC profile and simultaneous quantitative analysis of tingenone and pristimerin in four Celastraceae species using HPLC-UV-DAD-MS. Rev Bras Farmacogn2019; 29(2): 171–176.
47.
ElekofehintiOOOnunkunATOlaleyeTM. Cymbopogon citratus (DC.) Stapf mitigates ER-stress induced by streptozotocin in rats via down-regulation of GRP78 and up-regulation of Nrf2 signaling. J Ethnopharmacol2020; 262: 113130.
48.
OlumegbonLTLawalAOOluyedeDM, et al.Hesperetin protects against diesel exhaust particles-induced cardiovascular oxidative stress and inflammation in Wistar rats. Environ Sci Pollut Res2022; 29(35): 52574–52589.
49.
MoronkejiAEzeIGBejideRA, et al.Evaluation of herbal cocktail used in the treatment of malaria on liver tissue of adult Wistar rats. J Med Plants Res2018; 12(28): 508–521.
50.
FeldmanATWolfeD. Tissue processing and hematoxylin and eosin staining. Methods Mol Biol2014; 1180: 31–43.
51.
FatimaGRazaAMHadiN, et al.Cadmium in human diseases: it’s more than just a mere metal. Indian J Clin Biochem2019; 34(4): 371–378.
52.
AdeniyiTDMoronkejiARalph-OkhiriaOF. Ascorbate and alpha-tocopherol mitigate toxic pathological changes in adult Wistar rats exposed to cypermethrin. Folia Medica Indones2023; 59(4): 387–395.
53.
MoronkejiATemidayoABenitaA, et al.Methanolic leaf extract of Vernonia amygdalina mitigates cadmium-induced oxidative stress in the liver and kidney of adult male Wistar rats. Egypt J Basic Appl Sci2024; 11(1): 469–478.
54.
AkinwumiKAGbadegesinMAAboyewaJA, et al.Attenuation of potassium dichromate and sodium arsenite toxicities by methanol extract of Rauvolfia vomitoria in mice. J Basic Clin Physiol Pharmacol2022; 33(3): 255–264.
55.
AdeniyiTDAkinpeluMOmokehinde Oseni AkinlamiFO, et al.Evaluation of the combined extract of Rauwolfia vomitoria and Aframomum melegueta on the kidney and liver of adult male Wistar rats. Sokoto J Med Lab Sci2024; 9(2): 203–212.
56.
CheCTWangZJChowMSS, et al.Herb-herb combination for therapeutic enhancement and advancement: theory, practice and future perspectives. Molecules2013; 18(5): 5125–5141.
57.
LiYFXuBYAnR, et al.Protective effect of anisodamine in rats with glycerol-induced acute kidney injury. BMC Nephrol2019; 20(1): 1–14.
58.
OyeniranOHAdemiluyiAOObohG. Phenolic constituents and inhibitory effects of the leaf of Rauvolfia vomitoria Afzel on free radicals, cholinergic and monoaminergic enzymes in rat’s brain in vitro. J Basic Clin Physiol Pharmacol2021; 32(5): 987–994.
59.
JuangYPLiangPH. Biological and pharmacological effects of synthetic saponins. Molecules2020; 25(21): 4974.
60.
SzczurekA. Perspectives on tannins. Biomolecules2021; 11(3): 1–3.
