Exploration of phytochemicals and antihyperlipidemic effect of crateva religiosa bark: <i>in vivo</i> mechanistic approach for management of hyperlipidaemia

Singh, Monika; Sachdeva, Monika; Kumar, Nitin

doi:10.1590/s2175-97902026e24772

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Article • Braz. J. Pharm. Sci. 62 • 2026 • https://doi.org/10.1590/s2175-97902026e24772 linkcopy

Exploration of phytochemicals and antihyperlipidemic effect of crateva religiosa bark: in vivo mechanistic approach for management of hyperlipidaemia

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Abstract

The work investigated the presence of phytochemicals and antihyperlipidemic potential of the ethanolic extract of Crateva religiosa (CRETE). The extraction yield was found to be highest with ethanol (15.81% w/w), followed by ethyl acetate (11.98% w/w) and very poor in hexane (3.05% w/w), using as solvents of variable polarity. Quantitative phytochemical analysis revealed that CRETE consists of higher total phenolic content (81.19 µg/mg equivalent to gallic acid) and flavonoid contents (49.0 µg/mg quercetin equivalents) compared to the ethyl acetate extract. GC-MS analysis confirmed the presence of stigmasterol, gamma-sitosterol and lupeol as phytochemicals. In vivo studies demonstrated that 400 mg/kg of CRETE reduced the levels of triglycerides (155.9 ± 1.51 mg/dl), total cholesterol (234.27 ± 1.91 mg/dl) and low-density lipoprotein cholesterol (66.27 ± 2.07 mg/dl), while increased the level of high-density lipoprotein cholesterol (133.48 ± 3.72 mg/dl). Atherogenic indices were also improved significantly. CRETE restored hepatic architecture and reduced adipocyte size. CRETE also exhibited strong antioxidant effects by lowering malondialdehyde (MDA) levels and enhancing glutathione (GSH), superoxide dismutase (SOD) and catalase activities. Mechanistically, in comparison to control groups, CRETE inhibited HMG-CoA reductase activity (p < 0.0001) and up-regulated PPARγ (p < 0.01) and CCAAT/EBPα (p <0.05) expressions in adipocytes significantly.

Keywords:
Cholesterol diet; HMG-CoA reductase; Oxidative stress; Hypercholesterolemia; PPARγ; CCAAT/EBPα.

S.No.	Plant Extract	Total Phenol	Total Flavonoid
1	Ethyl acetate	29.47 ± 2.12	8.78 ±1.61
2	Ethanol extract (CRETE)	81.19 ± 1.26	49.08 ± 0.402

Peak	RT	Height	% Height	Area	% Area	Name of compound	Molecular formula	Molecular weight
1	29.18	4229238	0.84	10395944	0.81	Stigmasterol	C29H48O	412
2	29.69	14019571	2.79	35105600	2.73	Gamma sitosterol	C29H50O	414
3	30.58	34761880	6.93	102905062	7.99	Lupeol	C30H50O	426

Plasma Lipid Profile		Treatment groups
Parameter	Duration (Week)	Group I (Control)	Group II (Cholesterolrich diet induced control)	Group III (Standard)	Group IV (Receiving low dose of CRETE, (100 mg/kg)	Group V (Receiving medium dose of CRETE, (200 mg/kg)	Group VI (Receiving high dose of CRETE, (400 mg/kg)
TC (mg/dl)	0	93.76 ± 2.63	94.69 ± 2.67	97.47 ± 2.133	101.35 ± 2.09	92.58 ± 2.11	93.35 ± 3.19
	3rd	132.08 ± 1.88	261.06 ± 3.19 ***	244.13 ± 2.28***	252.63 ± 4.54 ***	251.98 ± 2.10 ***	242.85 ± 1.77 ***
	6th	139.97 ±11.82	326.4 ± 6.33 ***	262.37 ± 19.38 ***	292.92 ± 2.26***	271.62 ± 7.37 ***	254.28 ± 1.98 ***
	9th	127.24 ± 4.89	331.22 ± 1.97 ***	242.13 ± 4.37 ***	305.53 ± 12.48 ***	274.33 ± 3.83 ***	234.27 ± 1.91 ***
TG (mg/dl)	0	54.36 ± 3.31	56.99 ± 4.96	52.26 ± 1.44	51.32 ± 0.62	54.01 ± 2.41	54.25 ± 3.35
	3rd	63.31 ± 1.63	132.22 ± 2.58 ***	114.83 ± 2.32 ***	125.39 ± 6.48***	119.67 ± 5.55***	114.33 ± 1.81***
	6th	72.35 ± 1.76	141.83 ± 1.56 ***	122.53 ± 1.78 ***	135.42 ± 2.76 ***	124.37 ± 3.35 ***	121.03 ± 8.51 ***
	9th	82.45 ± 1.38	165.15 ±2.01***	156.57 ± 5.59 ***	161.45 ± 2.12 ***	159.92 ± 2.10 ***	155.9 ± 1.51 ***
HDL-c (mg/dl)	0	111.62 ± 4.77	95.78 ± 3.09**	97.8 ± 4.76**	99.1 ± 1.30 ^*	99.73 ± 6.89 ^*	99.15 ± 2.20^*
	3rd	108.6 ± 6.51	61.33 ± 1.18***	124.5 ± 2.10 **	100.92 ± 29.68	113.4 ±0.96	125.73 ± 4.76 ***
	6th	103.8 ± 10.26	54.55 ± 2.88***	128.43 ± 4.77 ***	102.46 ± 5.79	119.12 ± 3.51 **	123.27 ± 3.51***
	9th	61.33 ± 1.57	49.55 ± 6.36 **	134.03 ± 1.47***	113.1 ± 1.45 ***	124.85 ± 3.72***	133.48 ± 3.72 ***
LDL-c (mg/dl)	0	43.15 ± 2.60	43.03 ± 2.23	41.63 ± 1.63	40.89 ± 1.55***	41.39 ± 2.76	42.055 ± 4.71
	3rd	42.58 ± 2.86	65.24 ± 3.38 ***	62.27 ± 1.32 ***	61.58 ± 1.78***	61.06 ± 1.31***	59.94 ± 1.31***
	6th	40.57 ± 6.18	68.78 ± 3.93***	60.67 ± 3.89 ***	66.99 ± 2.13 ***	65.72 ± 1.90 ***	63.98 ± 1.77 ***
	9th	43.55 ± 3.78	72.88 ± 1.51***	54.74 ± 1.64 ***	70.03 ± 0.29 ***	68.93 ± 1.21 ***	66.27 ± 2.07 ***

Plasma Lipid Ratios				Treatment groups
Parameter	Duration (Week)	Control (Group I)	(Group II) Cholesterolrich diet induced control	Standard control (Group III)	Group IV (Receiving low dose of CRETE, (100 mg/kg)	Group V (Receiving medium dose of CRETE, (200 mg/kg)	Group VI (Receiving high dose of CRETE, (400 mg/kg)
AIP	0	0.32 ± 0.11	0.23 ± 0.02	0.28 ± 0.01	0.29 ±0.002	0.27 ± 0.007	0.26 ± 0.01
	3rd	0.23 ± 0.082	0.33 ± 0.003 ***	0.04 ± 0.003 *	0.19 ± 0.16 ***	0.023 ± 0.008 ***	0.04 ± 0.007 *
	6th	0.16 ± 0.01	0.42 ± 0.01 ***	0.02 ± 0.005	0.12 ± 0.002 ***	0.02 ± 0.01 *	0.01 ± 0.01
	9th	0.13 ± 0.02	0.53 ± 0.02 ***	0.07 ± 0.007	0.15 ± 0.003	0.11 ± 0.004	0.07 ± 0.003
AC	0	92.76 ± 1.07	93.69 ± 35.49	96.47 ± 0.87	100.35 ± 0.85	91.58 ± 0.86	92.35 ± 1.30
	3rd	131.08 ± 0.76	260.06 ± 14.10 ***	243.13 ± 0.93 ***	251.63 ± 1.86 ***	250.98 ± 3.10***	241.85 ± 0.72 ***
	6th	138.97 ±4.83	325.4 ± 2.09***	261.37 ± 7.91 ***	291.92 ± 0.92 ***	270.62 ± 3.01***	253.28 ± 0.81 ***
	9th	126.24 ± 1.10	330.23 ± 0.81***	241.13 ± 1.79 ***	304.53 ± 5.09 ***	273.33 ± 1.56***	233.27 ± 0.78 ***
CRI-I	0	0.84 ± 0.023	0.99 ± 0.018	0.999 ± 0.022	1.01 ± 0.010	0.93 ± 0.01	0.94 ± 0.01
	3rd	1.22 ± 0.03	4.26 ± 0.39 *	1.96 ± 0.023	5.59 ± 3.47 ***	2.22 ± 0.01	1.93 ± 0.03
	6th	1.36 ± 0.08	5.10 ± 0.15 ***	2.04 ± 0.065	2.86 ± 0.03	2.28 ± 0.05	2.06 ± 0.02
	9th	2.08 ± 0.053	6.77 ± 0.34 ***	1.81 ± 0.021	2.70 ± 0.05	2.20 ± 0.03	1.76 ± 0.01
CRI-II	0	0.39 ± 0.01	0.45 ± 0.01	0.43 ± 0.01	0.41 ± 0.01	0.42 ± 0.01	0.42 ± 0.17
	3rd	0.39 ± 0.02	1.06 ± 0.02 *	0.50 ± 0.005	1.32 ± 0.80 **	0.54 ± 0.004	0.48 ± 0.19
	6th	0.40 ± 0.3	1.27 ± 0.05**	0.47 ± 0.01	0.65 ± 0.01	0.55 ± 0.013	0.52 ± 0.21
	9th	0.71 ± 0.02	1.48 ± 0.07*	0.41 ± 0.005	0.62 ± 0.01	0.55 ± 0.008	0.50 ± 0.20

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Universidade de São Paulo, Faculdade de Ciências Farmacêuticas Av. Prof. Lineu Prestes, n. 580, 05508-000 S. Paulo/SP Brasil, Tel.: (55 11) 3091-3824 - São Paulo - SP - Brazil
E-mail: bjps@usp.br

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[1] The plasma lipid profile parameters including TC, TG, HDL-c and LDL-c for different treatment groups across four time points (0, 3^rd, 6^th, and 9^th weeks). Group I (Control) having no treatment, used as baseline for comparison. Group II (Cholesterol induced Control) treated with a substance expected to induce unfavourable lipid changes. Group III (Standard Control) received a standard treatment with known lipidmodulating effects. Group IV has low dose of CRETE (100 mg/kg). Group V treated with medium dose of CRETE (200 mg/kg). Group VI animals treated with high dose of CRETE (400 mg/kg). The data are presented as mean ± SEM with statistical comparisons to the control group indicated by asterisks (^*p < 0.05,

[TFN1] ^**
p < 0.01,

[TFN2] ^***
p < 0.001). Two-way ANOVA and Bonferroni’s post-hoc test was used for statistical analysis. The table highlights the changes in lipid profile parameters over the study duration, with significant differences observed between groups mainly at 3^rd, 6^th, and 9^th weeks). TC: Shows significant increases in the cholesterol induced control group compared to the control group, with considerably differences at later weeks in the test groups. TG: Level of TG elevated in the cholesterol induced control group but reductions in TG levels for the higher dose CRETE groups. HDL-c: Level of HDL-c decreased in the cholesterol induced control groups, but CRETE restored the level of this especially with high test dose. LDL-c: Significant increases observed in the cholesterol induced control groups, while CRETE-treated groups show more stable lipid levels.