The bioprospecting potential of <i>Clusia fluminensis</i> Planch. &amp; Triana: a scoping review

FARIA, GISELLE M.; LEMOS, ANA PATRICIA A.; ANHOLETI, MARIA C.; PAIVA, SELMA R.; AMORIM, LIDIA M.F.

doi:10.1590/0001-3765202320211605

person GISELLE M. FARIA

search and selection of the papers, categorization by bibliographic databases, writing of original draft, data analysis and organization of the results

schoolUniversidade Federal Fluminense, Instituto de Biologia, Departamento de Biologia Celular e Molecular, Rua Prof. Marcos Waldemar de Freitas Reis, Bloco M, 311, São Domingos, 24210-201 Niterói, RJ, Brazil

0000-0002-4287-1651

person ANA PATRICIA A. LEMOS

search and selection of the papers, categorization by bibliographic databases, figures design

schoolUniversidade Federal Fluminense, Instituto de Biologia, Departamento de Biologia Celular e Molecular, Rua Prof. Marcos Waldemar de Freitas Reis, Bloco M, 311, São Domingos, 24210-201 Niterói, RJ, Brazil

0000-0002-4119-9656

person MARIA C. ANHOLETI

reviewing and editing

schoolUniversidade Federal Fluminense, Faculdade de Farmácia, Departamento de Farmácia e Administração Farmacêutica, Rua Dr. Mario Vianna, 523, Santa Rosa, 24241-001 Niterói, RJ, Brazil

0000-0003-1552-9161

person SELMA R. PAIVA

reviewing and editing, project administration, funding acquisition

schoolUniversidade Federal Fluminense, Instituto de Biologia, Departamento de Biologia Geral, Rua Prof. Marcos Waldemar de Freitas Reis, Bloco M, 111, São Domingos, 24210-201 Niterói, RJ, BrazilschoolPrograma de Pós-Graduação em Ciências Aplicadas a Produtos para Saúde, Universidade Federal Fluminense, Faculdade de Farmácia, Rua Dr. Mario Vianna, 523, Santa Rosa, 24241-001 Niterói, RJ, Brazil

0000-0002-8295-7011

person LIDIA M.F. AMORIM

conceptualization, reviewing and editing, data analysis, supervision, project administration, funding acquisition

schoolUniversidade Federal Fluminense, Instituto de Biologia, Departamento de Biologia Celular e Molecular, Rua Prof. Marcos Waldemar de Freitas Reis, Bloco M, 311, São Domingos, 24210-201 Niterói, RJ, Brazil

0000-0001-7282-9748

Correspondence to: Lídia Amorim E-mail:
amorimlidia@id.uff.br

Figures (2)
Tables (3)

Thumbnail

Figure 1 Flow diagram of literature search results and its critical appraisal. The flowchart a) shows the steps adopted on records selection. The superpositions of the captured records from four databases are depicted in diagram b). The critical appraisal (CA; H: high, M: moderate) of the selected studies according to the main research field (1: Phytochemistry, 2: Bioactivity) is shown in c).

Thumbnail

Figure 2 Antibothropic activity of Clusia fluminensis extracts assayed in vitro and in vivo. a) In vitro assays were performed in which the venoms of Bothrops jararaca or B. jararacussu were pre-incubated with plant extracts or isolated molecules and then with: (i) azocasein, (ii) plasma or (iii) a mixture of human red blood cells and hen’s egg yolk emulsion to determine, respectively (i) proteolytic inhibition, (ii) clotting time and (iii) antihemolytic activity. Hemolysis induced by the venom of B. jararacussu was not tested, since this venom has low hemolytic activity. b) In vivo antibothropic evaluation was performed using pre-incubation, treatment or prevention protocols using distinct routes of administration (*). As with the in vitro assays, in the in vivo incubation protocol, venom was pre-incubated with the plant extracts before injection in mice. For the treatment protocol, the mice were pre-injected with venom and then treated with each extract. For the prevention protocol, mice were fed with the extracts before the venom injection. Distinct routes of administration for snake venoms and plant extracts were as follows: top (topical), p.o. (oral), s.c. (subcutaneous), i.v. (intravenous), i.m. (intramuscular), i.p. (intraperitoneal), i.d. (intradermal). Positive control groups received snake venom mixed with saline, and negative controls received plant extracts alone. Myotoxicity assay was only performed for B. jararacussu envenomation, due to its marked effect compared to B. jararaca.

Thumbnail

Table I Clusia fluminensis phytochemical profile.

Thumbnail

Table II Overview of the biological activity of Clusia fluminensis extracts and isolated compounds.

Thumbnail

Table III Anti-Bothrops snake venom activity of organic and aqueous extracts of Clusia fluminensis.

Reference	Plant Organ	Solvent used on Extraction	Chemical Class *	Compound	Content	Unit	Identification / Quantification method **
Guimarães et al. (2021)	Leaves	Methanol	Total phenolics	-	16.29 ± 0.66 (pistillate individuals)	mg/g	Spectrophotometry (760 nm)
			Total phenolics	-	10.15 ± 0.31 (staminate individuals)	mg/g	Spectrophotometry (760 nm)
			Flavonoids	-	7.54 ± 0.09 (pistillate individuals)	mg/g	Spectrophotometry (760 nm)
			Flavonoids	-	6.75 ± 0.04 (staminate individuals)	mg/g	Spectrophotometry (760 nm)
Mazza et al. (2019)	Arils of the fruits with seeds	Sulfuric acid 0.05 M	Vitamin (^a)	Ascorbic acid	3.77 ± 0.82	mg/100 g	HPLC (ion exchange chromatography) / Spectrophotometry (242.6 nm)
		Methanol : Acetic Acid	Phenolic acids (^b)	Protocatechuic acid	115.14 ± 58.23	µg / g	HPLC-DAD (C18) / Spectrophotometry (270 - 310 nm)
				p-hydroxybenzoic acid	11.43 ± 0.32	µg / g
				p-hydroxycinnamic acid	5.97 ± 0.41	µg / g
		Methanol : Acetic Acid and alkaline or acid hydrolysis	Total phenolic acids (^b)	Protocatechuic acid	55.82 ± 12.23	µg / g
				p-hydroxybenzoic acid	16.76 ± 1.06	µg / g
				p-hydroxycinnamic acid	49.03 ± 12.69	µg / g
		Methanol : H₂O	Flavonoids (^c)	Rhamnetin and rhamnetin derivative	-		HPLC-DAD (C18) / Spectrophotometry (270 - 310 nm)
		Acetone : Petroleum ether	Carotenoids (^d)	Zeaxanthin	823	µg / g	HPLC UV-VIS / Spectrophotometry (450 nm)
				β-cryptoxanthin	-
				Lutein	-
Camara et al. (2018)	Fruit latex	Methanolic latex collection from fresh cut fruits	Fatty acid derivative	Tetradecane	7.82	%	GC - FID / GC - MS
			Terpenoids	α-copaene	8.69	%	GC - FID / GC - MS
				β-caryophyllene	35.61	%
				α-humulene	2.11	%
				Germacrene D	8.78	%
				β-selinene	12.44	%
				α-selinene	6.56	%
				trans-β-guaiene	2.18	%
				Spathulenol	6.37	%
				Caryophyllene Oxide	3.45	%
				10-epi-γ-eudesmol	5.54	%
			Benzenoids	p-anysaldehyde	0.36	%	GC - FID / GC - MS
			Benzenoids	Acetophenone	traces	-	GC - FID / GC - MS
Anholeti et al. (2017)	Leaves wax	Chloroform	Terpenoids	Epifriedelinol	23.98 to 70	%	GC-MS
				Friedelin	58.37	%
				α a- β amyrin	-	-
				Lupenone	-	-
			Steroids	Sitosterol	-	-	GC-MS
			Steroids	Stigmasterol	-	-	GC-MS
Duprat et al. (2017)	Fruit	Hexane	Terpenoids	Lanosterol	40.6	%	GC - MS
			Terpenoids	Lanosterol isomers	10.73	%	GC - MS
			Fatty acids	Palmitic acid	-	-	GC - MS
			Fatty acids	Oleic acid	-	-	GC - MS
Anholeti et al. (2015)	Flower	Hexane	Polyisoprenylated benzophenone	Clusianone tautomeric pair	54.85	%	GC-MS
Anholeti et al. (2015)	Flower	Hexane	Terpenoid	Lanosterol	9.74	%	GC-MS
Meneses et al. (2015)	Flower	Hexane	Terpenoids	Lanosterol and isomers	-	-	GC-MS
Oliveira et al. (2014)	Fruit	Hexane	Terpenoid	Lanosterol	-	-	GC-MS
Silva & Paiva (2012)	Fruit	Acetone	Flavonoids	-	13.93 ± 0.21	%	Colorimetric (415 nm)
	Stem	Acetone		-	9.12 ± 1.14	%
	Fruit	Methanol		-	10.68 ± 0.58	%
	Stem			-	9.82 ± 0.53	%
	Leaves			-	8.07 ± 1.70	%
Silva et al. (2012)	Flower	Hexane	Polyisoprenylated benzophenone	Clusianone tautomeric pair	6.9 yield	%	GC/MS
Porto et al. (2001)	Flower resin	Fresh material methylation with diazomethane a- diethyl ether	Polyisoprenylated benzophenones	Clusianone	37	%	RP-HPLC
				Spiritone	10	%
				Weddellianone/ Lanceolatone	6.7	%
Nogueira et al. (2001)	Flower petals essential oils	Fresh material distillation water with dichloromethane	Terpenoids	Sesquiterpenes	64.1	%	GC-MS
				Oxygen-containng sesquiterpenes	29.4	%
				Monoterpenes	0.5	%
				Oxygen-containng monoterpenes	0.1	%
			Carboxylic acids	Carboxylic acids	2	%	GC-MS
			Long chain hydrocarbons	Oxygen-containing long chain hydrocarbons	0.2	%	GC-MS
			Long chain hydrocarbons	Long chain hydrocarbons	0.1	%	GC-MS
Nagem et al. (1993)	Leaves	-	Triterpenoids	Lupenone	640	µg / g	-
				Amyrin	617.14	µg / g
				α and- β friedelinol	328.57	µg / g
				Friedelin	71.42	µg / g
			Steroid	Sitosterol	457.14	µg / g
			Alcohol of fatty acid	n-octacosanol	257.14	µg / g
			Long chain hydrocarbons	Tricosane	642.86	µg / g

Biological Effect		Hexane				Dichloromethane	Acetone		Methanol			Water			Isolated compounds
Biological Effect		Leaves	Flower	Fruit	Stem	Flower	Fruit	Stem	Leaves	Fruit	Stem	Leaves	Fruit	Stem	Clusianone	Lanosterol
Anti-viral*	HSV-1 Inhibition	√	√	√	√	-	√	√	√	√	√	-	-	-	√	√
Anti-viral*	HIV-RT Inhibition	Ø	-	Ø	Ø	-	-	Ø	√	Ø	√	-	-	-	√	√
Insecticidal**	Aedes aegypti	-	√	Ø	-	-	-	-	-	-	-	-	-	-	√	Ø
	Dysdercus peruvianus	-	√	√	-	-	-	-	-	-	-	-	-	-	√	√
	Oncopeltus fasciatus	-	√	√		-	-	-	-	-	-	-	-	-	√	√
Snake venom antidote ***	Bothrops jararaca	√	√	√	√	√	√	√	√	√	√	√	√	√	√	√
Snake venom antidote ***	Bothrops jararacussu	-	-	-	-	-	-	-	-	-	-	√	√	√	-	-

Protocol	Biological Assay *()**	Model	Administration Route / Venom:plant ratio (w:w) ()**	Leaf			Stem				Fruit				Flower
Protocol	Biological Assay *()**	Model	Administration Route / Venom:plant ratio (w:w) ()**	Hex	MeOH	H ₂ O	Hex	Acet	MeOH	H ₂ O	Hex	Acet	MeOH	H ₂ O	Hex	CH ₂ Cl ₂
Pre-incubation Protocol	Proteolysis Reduction (%)	Bja	NA / 1:20	44	52	90	34	78	91	40	19	100	100	100	75	47
	Proteolysis Reduction (%)	Bju	NA / 1:20	-	-	58	-	-	-	28	-	-	-	100	-	-
	Hemolysis Reduction (%)	Bja	NA / 1:20	74	71	50	41	93	99	22	24	32	59	100	42	9
	Clotting Times (sec)	Bja	NA / 1:20	84	85	60	73	171	150	89	89	107	100	100	107	96
	Clotting Times (sec)	Bju	NA/ 1:5	-	-	70	-	-	-	76	-	-	-	82	-	-
	Hemorrhage Reduction (%)	Bja	i.d. / 1:2, 1:5 or 1:20(^c)	Ø	Ø	58	Ø	Ø	Ø	24	50	100	Ø	100	Ø	Ø
	Hemorrhage Reduction (%)	Bju	i.d. / 1:20	-	-	74	-	-	-	100	-	-	-	100	-	-
	Edema Reduction (%)	Bja	s.c. / 1:10	-	-	84	-	-	-	80	-	-	-	80	-	-
	Edema Reduction (%)	Bju	s.c. / 1:10	-	-	7	-	-	-	63	-	-	-	100	-	-
	Miotoxicity Reduction (CK Units)(^a)	Bju	i.m. / 1:10	-	-	1400	-	-	-	920	-	-	-	1360	-	-
	Survival Time (min)(^b)	Bja	i.p.; i.v./ 1:1	-	-	360 ± 3	-	-	-	360 ± 5	-	-	-	360 ± 4	-	-
	Survival Time (min)(^b)	Bju	i.v. / 1:1	-	-	145 ± 4	-	-	-	72 ± 7	-	-	-	360 ± 2	-	-
Treatment Protocol	Edema Reduction (%)	Bja	p.o. / 1:10	-	-	0	-	-	-	40	-	-	-	25	-	-
	Edema Reduction (%)	Bju	p.o. / 1:10	-	-	16	-	-	-	39	-	-	-	32	-	-
	Survival Time (min)	Bja	i.p./ 1:1 or 1:10(^d)	-	-	75 ± 0.7	-	900	900	180 ± 0.9	-	-	-	70 ± 0.6	-	-
	Survival Time (min)	Bju	iv / 1:1	-	-	70 ± 9	-	-	-	70 ± 6	-	-	-	360 ± 4	-	-
	Hemorrhage Reduction (%)	Bja	i.v. / 1:20	-	-	51	-	-	-	60	-	-	-	41	-	-
			s.c or i.d./ 1:2 or 1:20(^e)	-	-	51	-	-	-	60	10	10	-	41	-	-
			topical	-	-	-	-	-	-	-	-	-	-	50	-	-
		Bju	i.v. / 1:20	-	-	35	-	-	-	45	-	-	-	36	-	-
			s.c. / 1:20	-	-	35	-	-	-	45	-	-	-	36	-	-
			topical	-	-	-	-	-	-	-	-	-	-	55	-	-
Prevention Protocol	Hemorrhage Reduction (%)	Bja	p.o. / 1:20	-	-	42	-	-	-	Ø	-	-	-	43	-	-
Prevention Protocol	Hemorrhage Reduction (%)	Bju	p.o. / 1:20	-	-	46	-	-	-	50	-	-	-	35	-	-

[1] - unavailable in the reference. * Method of analysis described by (a) Rosa et al. (2007); (b) Mattila & Kumpulainen (2002); (c) Klump et al. (2001); (d) Rodriguez-Amaya (1999); Pacheco et al. (2014). ** DAD (diode-array detection); FID (Flame Ionization Detector); GC (gas-chromatography); HPLC (High performance liquid chromatography); HSCCC (High-speed counter current chromatography); MS (Mass-spectrometry); RP (Reverse Phase); UV-VIS (ultraviolet- visible).

The bioprospecting potential of Clusia fluminensis Planch. & Triana: a scoping review