Uncaria tomentosa Exerts Extensive Anti-Neoplastic Effects against the Walker-256 Tumour by Modulating Oxidative Stress and Not by Alkaloid Activity

Abstract

This study aimed to compare the anti-neoplastic effects of an Uncaria tomentosa (UT) brute hydroethanolic (BHE) extract with those of two fractions derived from it. These fractions are choroformic (CHCl3) and n-butanolic (BuOH), rich in pentacyclic oxindole alkaloids (POA) and antioxidant substances, respectively. The cancer model was the subcutaneous inoculation of Walker-256 tumour cells in the pelvic limb of male Wistar rat. Subsequently to the inoculation, gavage with BHE extract (50 mg.kg−1) or its fractions (as per the yield of the fractioning process) or vehicle (Control) was performed during 14 days. Baseline values, corresponding to individuals without tumour or treatment with UT, were also included. After treatment, tumour volume and mass, plasma biochemistry, oxidative stress in liver and tumour, TNF-α level in liver and tumour homogenates, and survival rates were analysed. Both the BHE extract and its BuOH fraction successfully reduced tumour weight and volume, and modulated anti-oxidant systems. The hepatic TNF-α level indicated a greater effect from the BHE extract as compared to its BuOH fraction. Importantly, both the BHE extract and its BuOH fraction increased the survival time of the tumour-bearing animals. Inversely, the CHCl3 fraction was ineffective. These data represent an in vivo demonstration of the importance of the modulation of oxidative stress as part of the anti-neoplastic activity of UT, as well as constitute evidence of the lack of activity of isolated POAs in the primary tumour of this tumour lineage. These effects are possibly resulting from a synergic combination of substances, most of them with antioxidant properties.

Medicinal uses, phytochemistry and pharmacology of the genus Uncaria

“…Among Uncaria species, U. tomentosa was considered as effective antitumor candidate to inhibit cancer cells growth, such as HL-60 (leukemia) (Cheng et al, 2007;Bacher et al, 2006), MCF7 and MT-3 (breast) (Riva et al, 2001;Sun et al, 2012a;Pilarski et al, 2010;García Giménez et al, 2010), (Dreifuss et al, 2013) 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 Xian et al, 2014Xian et al, et al, 2007. The correlations between pharmacological properties of U. tomentosa and active compounds revealed that oxindole alkaloids and triterpenes are major bioactive constituents.…”

“…The sole substances responsible for its anti-neoplastic effect was a synergic combination of substances based on antioxidant activity rather than just oxindole alkaloids (Coussens and Werb, 2002;Mantovani et al, 2008;Dreifuss et al, 2013).…”

Uncaria tomentosa and Uncaria guianensis an agronomic history to be written

“…In addition to the ethnopharmacological data, various pharmacological tests performed in vitro and in vivo confirmed its antioxidant ( DREIFUSS et al, 2013), anticancer (PILARSKI et al, 2010, anti inflammatory (ROJAS-DURAN et al, 2012), antimicrobial (CCAHUANA-VASQUEZ et al, 2007, antiherpetic (CAON et al, 2014), contraceptive (NOGUEIRA NETO et al, 2011), neuroprotective (SHI et al, 2013), and antidiabetic (DOMINGUES et al, 2011) activities.…”

Uncaria tomentosa (Willd. ex Schult.) DC.: A Review on Chemical Constituents and Biological Activities

“…Cat's claw contains several active compositions including ajmalicine, campesterol, carboxyl alkyl esters, akuammigine, sitosterols, rutin, chlorogenic acid, speciophylline, catechin, cinchonain [15], corynoxeine, harman, daucosterol, epicatechin, hirsuteine, corynantheine, hirsutine, loganic acid, mitraphylline, iso-pteropodine, oleanolic acid, ursolic acid, lyaloside [16], rhynchophylline, palmitoleic acid, pteropodine quinovic acid glycosides, procyanidins [10], stigmasterol, 3,4-dehydro-5-carboxystrictosidine, vaccenic acid, uncarine A thru F, and strictosidines [10,17]. Moreover, other reports revealed that various compounds other than oxindole alkaloids such as rotundifoline and isorotundifolune, coumarins, flavonoids, quinovic acid glycosides, and triterpenes may be responsible for the cat's claw medicinal effects [18,19].…”