Several species of Cuphea are used medicinally and are reported to have cardioprotective, diuretic, and antihypertensive properties. In Brazil, Cuphea species are collectively called “sete-sangrias” due to their similar appearances and are also used interchangeably for the same therapeutic purposes. So the aim of the study was to characterize morphoanatomy of leaves and stems, evaluate the safety, and investigate the diuretic, hypotensive, vasodilatory, and antioxidant properties of ethanol-soluble fraction of Cuphea calophylla var. mesostemon (Koehne) S.A. Graham. Initially, the morphoanatomical characterization of the leaves and stems of C. calophylla var. mesostemon was performed. For the pharmacological evaluation, the ethanol-soluble fraction from Cuphea calophylla (ESCC) was obtained and chemically characterized by high-performance liquid chromatography coupled with a diode array detector and tandem mass spectrometry techniques. Then, acute toxicity, diuretic, hypotensive, antioxidant, and vasodilatory effects were evaluated in Wistar rats. The main chemical compounds identified from ESCC were gallic acid derivatives, ellagitannins, and flavonoids. ESCC showed no acute toxic effect. ESCC showed no acute toxic effect and the estimated median lethal dose (LD50) was above 2000 mg/kg. ESCC treatment (30, 100, and 300 mg/kg) did not present any significant acute diuretic or hypotensive effects. However, an important reduction in the elimination of electrolytes was observed after the acute administration, and a significant increase in renal sodium elimination was observed after 7 days of treatment. In the cardiac tissue, the groups treated with ESCC presented significant increase in superoxide dismutase activity.
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References
1.
OliveiraC, CabriniD, SantosE, MarquesM, BuchiD: Canova medication and medicinal plants in south of Brazil. In: Trends and Developments in Ethnopharmacology (PretoriusR, ed.). Research Signpost, Trivandrum, India, 2008, pp. 1–17.
2.
WoschL, ImigD, CerviA, MouraB, BudelJ, SantosC: Comparative study of Passiflora taxa leaves: I. A morpho-anatomic profile. Rev Bras Farmacogn, 2015; 25:328–343.
3.
ToloueiS, PaloziR, TirloniC, MarquesA, SchaedlerM, GuarnierL, SilvaA, AlmeidaV, BudelJ, SouzaR, SantosA, NocchiS, SilvaD, DalsenterP, Gasparotto-JuniorA: Anchietea pyrifolia A. St.-Hil. as a cardiovascular-endowed species: A whole-biological investigation. J Med Food, 2019; 22:393–407.
4.
BolsonM, HeflerSM, Dall'Oglio ChavesEI, Gasparotto JuniorA, Cardozo JuniorEL: Ethno-medicinal study of plants used for treatment of human ailments, with residents of the surrounding region of forest fragments of Paraná, Brazil. J Ethnopharmacol, 2015; 161:1–10.
5.
MenetrierJV, BonkoskiVR, MedeirosKA, EstevanDA, PaloziRAC, LíveroFADR, VelasquezLG, LourençoELB, Gasparotto JuniorA: Ethnomedicinal plants used for the treatment of cardiovascular diseases by healers in the Southwestern state of Paraná, Brazil, and their validation based on scientific pharmacological data. J Relig Health, 2019; [Epub ahead of print]; DOI: 10.1007/s10943-019-00960-1.
6.
KrepskyP, IsidórioR, Souza-FIlhoJ, CôrtesS, BragaF: Chemical composition and vasodilatation induced by Cuphea carthagenensis preparations. Phytomedicine, 2012; 19:953–957.
7.
BarbozaL, LíveroF, PrandoT, RibeiroR, LourençoE, BudelJ, SouzaL, AccoA, DalsenterP, Gasparotto-JuniorA: Atheroprotective effects of Cuphea carthagenensis (Jacq.) J.F. Macbr. in New Zealand rabbits fed with cholesterol-rich diet. J Ethnopharmacol, 2016; 187:134–145.
8.
SchaedlerM, PaloziR, TirloniC, SilvaA, AraujoV, LourençoE, SouzaL, LíveroF, Gasparotto-JuniorA: Redox regulation and NO/cGMP plus K+ channel activation contributes to cardiorenal protection induced by Cuphea carthagenensis (Jacq.) J.F. Macbr. in ovariectomized hypertensive rats. Phytomedicine, 2018; 51:7–19.
9.
Ramírez-AterhortúaA, Morales-AgudeloL, OsorioE, Lara-GuzmánA: The traditional medicinal plants Cuphea calophylla, Tibouchina kingii, and Pseudo lephantopus spiralis attenuate inflammatory and oxidative mediators. Evid Based Complement Alternat Med, 2018 [Epub ahead of print]; DOI: 10.1155/2018/1953726.
10.
JiménezN, Carrilo-HormazaL, PujolA, ÁlzateF, OsorioE, Lara-GuzmanO: Antioxidant capacity and phenolic content of commonly used anti-inflammatory medicinal plants in Colombia. Ind Crop Prod, 2015; 70:272–279.
11.
FilichkinS, SlabaughM, KnappS: New FATB thioesterases from a high-laurate Cuphea species: Functional and complementation analyses. Eur J Lipid Sci Tech, 2006; 108:979–990.
12.
PhippenW, IsbellT, PhippenM: Total seed oil and fatty acid methyl ester contents of Cuphea accessions. Ind Crop Prod, 2006; 24:52–59.
13.
GrahamS, JoséG, MuradA, RechE, CavalcantiT, InglisP: Patterns of fatty acid composition in seed oils of Cuphea, with new records from Brazil and Mexico. Ind Crop Prod, 2016; 87:379–391.
14.
JohansenD: Plant Microtechnique. McGraw Hill Book, New York, 1940.
15.
BerlynG, MikscheJ: Botanical Microtechnique and Cytochemistry. Iowa State University, Ames, Iowa, 1976, pp. 311–319.
16.
RoeserK: The needle of the black pine mass product and nature's work of art [in German]. Mikrokosmos, 1972; 61:33–36.
17.
Farmacopeia Brasileira: Volume 1. Agência Nacional de Vigilância Sanitária (ANVISA), Brasília, Brazil, 2019.
18.
FosterA: Practical Plant Anatomy. 2nd ed. D. Van Nostrand, Princeton, NJ, 1949.
19.
SassJ: Botanical Microtechnique. Iowa State University, Ames, Iowa, 1951, p. 228.
20.
Organisation for Economic Co-operation and Development (OECD):. Guidelines for testing of chemical, guideline 425. In: Acute Oral Toxicity-Up-and-Down-Procedure (UDP) (OECD, ed.). OECD, Paris, France, 2008, pp. 1–26.
21.
MaloneM, RobichaudR: A hippocratic screen for pure or crude drug materials. J Nat Prod, 1962; 25:320–331.
22.
KauS, KeddieJ, AndrewsD: A method for screening diuretic agents in the rat. J Pharmacol Methods, 1984; 11:67–75.
23.
GaoS, ZhaoG, LuoG, YangT, ShenJ: Antioxidant effects of superoxide dismutase and horseradish peroxidase on LPO. Ann N Y Acad Sci, 1988; 864:284–287.
24.
SedlakJ, LindsayR: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem, 1968; 25:192–205.
25.
BeersR, SizerI: A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem, 1952; 195:133–140.
26.
McGregorD: The effect of sympathetic nerve stimulation of vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J Physiol, 1965; 177:21–30.
27.
SantosV, FrancoC, AmanoE, Messias-ReasonI, BudelJ: Anatomical investigations of Piper amalago (jaborandi-manso) for the quality control. Rev Bras Farmacogn, 2015; 25:85–91.
28.
HomemI, BobekV, SzaboE, BudelJ, RamanV, OliveiraV, MiguelO: Anatomy and histochemistry of leaf and stem of Brazilian endemic species Mollinedia clavigera Tul. Braz Arch Biol Technol, 2020; 63 [Epub ahead of print]; DOI: 10.1590/1678-4324-2020180717.
29.
MigaczI, RaeskiP, AlmeidaV, RamanV, NisgoskiS, MunizG, FaragoP, KhanI, BudelJ: Comparative leaf morpho-anatomy of six species of Eucalyptus cultivated in Brazil. Rev Bras Farmacogn, 2018; 28:273–281.
30.
AmarasingheV, GrahamS, GrahamA: Trichome morphology in the genus Cuphea (Lythraceae). Bot Gaz, 1991; 152:77–90.
31.
LusaM, BonaC: Morphoanatomical and histochemical characterization of Cuphea carthagenensis (Jacq.) JF Macbr. (Lythraceae) [in Latin]. Acta Bot Bras, 2011; 25:517–527.
32.
LittleS, StockeyR, KeatingR: Duabanga-like leaves from the Middle Eocene Princeton chert and comparative leaf histology of Lythraceae sensu lato. Am J Bot, 2004; 91:1126–1139.
33.
UptonR, GraffA, JolliffeG, LängerR, WilliamsonE: American Herbal Pharmacopoeia: Botanical Pharmacognosy-Microscopic Characterization of Botanical Medicines. Boca Raton, FL: CRC Press, 2016.
34.
LeeJ, KimS, NamgungH, JoIH, BaoC, ChoiHK, AuhJH, LeeHJ: Ellagic acid identified through metabolomic analysis is an active metabolite in strawberry (‘seolhyang’) regulating lipopolysaccharide-induced inflammation. J Agric Food Chem, 2013; 62:3954–3962.
35.
MaldiniM, MontoroP, PizzaC: Phenolic compounds from Byrsonima crassifolia L. bark: Phytochemical investigation and quantitative analysis by LC-ESI MS/MS. J Pharm Biomed Anal, 2011; 56:1–6.
36.
HsuF, HuangW, WuT, LeeM, ChenL, LuH, HouW, LinM: Evaluation of antioxidant and free radical scavenging capacities of polyphenolics from pods of Caesalpinia pulcherrima. Int J Mol Sci, 2012; 13:6073–6088.
37.
ReichertC, SilvaD, CarolloC, Weffort-SantosA, SantosC: Metabolic profiling and correlation analysis for the determination of killer compounds of proliferating and clonogenic HRT-18 colon cancer cells from Lafoensia pacari. J Ethnopharmacol, 2018; 224:541–552.
38.
NguyenD, SeoU, ZhaoB, LeD, SeongS, ChoiJ, MinB, WooM: Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities. Bioorg Chem, 2017; 72:293–300.
39.
BaiN, HeK, RollerM, ZhengB, ChenX, ShaoZ, PengT, ZhengQ: Active compounds from Lagerstroemia speciosa, insulin-like glucose uptake-stimulatory/inhibitory and adipocyte differentiation-inhibitory activities in 3t3–l1 cells. J Agric Food Chem, 2008; 56:11668–11674.
40.
BadrA, El-DemerdashE, KhalifaA, GhoneimA, AyouN, Abdel-NaimA: Rubus sanctus protects against carbon tetrachloride-induced toxicity in rat isolated hepatocytes: isolation and characterization of its galloylated flavonoids. J Pharm Pharmacol, 2009; 61:1511–1520.
41.
IslamovR, KustovaT, NersesyanA, IlinA: Subchronic toxicity of the new iodine complex in dogs and rats. Front Vet Sci, 2020; 7:184.
42.
DybingE, DoeJ, GrotenJ, KleinerJ, O'BrienJ, RenwickAG, SchlatterJ, SteinbergP, TritscherA, WalkerR, YounesM: Hazard characterisation of chemicals in food and diet. dose response, mechanisms and extrapolation issues. Food Chem Toxicol, 2002; 40:237–282.
43.
MarcondesF, BianchiF, TannoA: Determination of the estrous cycle phases of rats: Some helpful considerations. Braz J Biol, 2002; 62:609–614.
44.
BiavattiM, FariasC, CurtiusF, BrasilL, HortS, SchusterL, LeiteS, PradoS: Preliminary studies on Campomanesia xanthocarpa (Berg.) and Cuphea carthagensis (Jacq.) J.F. Macbr. aqueous extract: Weight control and biochemical parameters. J Ethnopharmacol, 2004; 93:385–389.
45.
EspinosaJ, GarcíaO, ValenciaG, LinaresE, ByeR, RomeroI: Evidence of the anti-Helicobacter pylori, gastroprotective and anti-inflammatory activities of Cuphea aequipetala infusion. J Ethnopharmacol, 2014; 151:990–998.
46.
PrandoT, BarbozaL, GasparottoF, AraújoV, TirloniC, SouzaL, LourençoE, Gasparotto-JuniorA: Ethnopharmacological investigation of the diuretic and hemodynamic properties of native species of the Brazilian biodiversity. J Ethnopharmacol, 2015; 174:369–378.
47.
Gasparotto-JuniorA, BoffoM, LourençoE, StefanelloM, KassuyaC, MarquesM: Natriuretic and diuretic effects of Tropaeolum majus (Tropaeolaceae) in rats. J Ethnopharmacol, 2009; 122:517–522.
48.
BalmacedaR, CardinaliF, ThevenonM, SantoM: Diuretic effect of Cuphea glutinosa Cham. et Schltdl (Lythraceae) in Wistar rats. Dominguezia, 2018; 34:45–51.
49.
BragaF, WagnerH, LombardiJ, OliveiraA: Screening the Brazilian flora for antihypertensive plant species for in vitro angiotensin-I-converting enzyme inhibiting activity. Phytomedicine, 2000; 7:245–250.
50.
ZagoA, CarvalhoF, GutierresJ, BohnertC, FernandesM, MorandiniL, CoelhoH, FogaçaA, AndradeC, MostardeiroM, DalcolI, MorelA: A phytochemical study of the Cuphea glutinosa from Southern Brazil: Na+, K+-ATPase activity inhibition and antioxidant properties. Nat Prod Res, 2018; 1–6.
51.
DufourDR: Alanine aminotransferase: is it healthy to be “normal”?. Hepatology, 2009; 50:1699–1701.
52.
RiveraS, MartinJ, LandryJ: Acute and chronic hypertension: What clinicians need to know for diagnosis and management. Crit Care Nurs Clin North Am, 2019; 31:97–108.
53.
SchuldtE, CklessK, SimasM, FariasM, Ribeiro-do-ValleR: Butanolic fraction from Cuphea carthagenensis Jacq. McBride relaxes rat thoracic aorta through endothelium-dependent and endothelium-independent mechanisms. J Cardiovasc Pharmacol, 2000; 35:234–239.
54.
BadhaniB, SharmaN, KakkarR: Gallic acid: A versatile antioxidant with promising therapeutic and industrial applications. RSC Adv, 2015; 35:27540–27557.
55.
KimD, LeeK, LeeH, LeeC: Vitamin C equivalent antioxidant capacity (VCEAC) of phenolic phytochemicals. J Agric Food Chem, 2002; 50:3713–3717.
56.
KaurM, VelmuruganB, RajamanickamS, AgarwalR, AgarwalC: Gallic acid, an active constituent of grape seed extract, exhibits anti-proliferative, pro-apoptotic and anti-tumorigenic effects against prostate carcinoma xenograft growth in nude mice. Pharm Res, 2009; 26:2133–2140.
57.
PriscillaD, PrinceP: Cardioprotective effect of gallic acid on cardiac troponin-T, cardiac marker enzymes, LPO products and antioxidants in experimentally induced myocardial infarction in Wistar rats. Chem Biol Interact, 2009; 179:118–124.
58.
JinL, LinM, PiaoZ, ChoJ, KimG, ChoiS, RuyY, SunS, KeeH, JeongM: Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-l-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2. J Hypertens, 2017; 35:1502–1512.
59.
AkdemirF, GülçinI, KaragözB, SosluR, AlwaselS: Comparative study on the antioxidant effects of hesperidin and ellagic acid against skeletal muscle ischemia/reperfusion injury. J Enzyme Inhib Med Chem, 2016; 31:114–118:2016.
60.
ZekaK, RupareliaK, ContinenzaM, StagosD, VeglioF, ArooR: Petals of Crocus sativus L. as a potential source of the antioxidants crocin and kaempferol. Fitoterapia, 2015; 107:128–134.
61.
EngQ, ThanikachalamP, RamamurthS: Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases. J Ethnopharmacol, 2018; 210:296–310.
