Anti-inflammatory and antitumor activities of the chloroform extract and anti-inflammatory effect of the three diterpenes isolated from Salvia ballotiflora Benth

Abstract

Background Drugs used for the treatment of diseases associated with chronic inflammation, such as cancer and rheumatoid arthritis have the potential to cause undesirable side-effects, which might result in patients ending treatment prematurely. However, plants are a viable option for the treatment of inflammatory diseases. In this study, we assessed the in vivo and in vitro anti-inflammatory activity, and the antitumor effects of the chloroform extract of Salvia ballotiflora (ECL). The pro-apoptotic effects of ECL in CT26 cells were also determined. Methods The chloroform extract of Salvia ballotiflora (ECL) was standardized using 19-deoxyicetexone (DEOX) as a phytochemical marker. The anti-inflammatory activity of ECL was determined on acute and chronic inflammatory models using the TPA-induced mouse ear edema assay. The antitumor activity of ECL was evaluated by the subcutaneous inoculation of CT26 cells on the back of Balb/c mice. In vitro CT26 cell death induced by ECL was determined by Annexin V/propidium iodide staining assay using flow cytometry. ECL and the diterpenes isolated from the chloroform extract included 19-deoxyicetexone (DEOX), icetexone (ICT), and 7,20-dihydroanastomosine (DAM), which were tested in LPS-stimulated J774A.1 macrophages to quantify pro-inflammatory cytokine levels. The in vitro anti-arthritic activity of ECL was determined using the bovine serum protein (BSP) denaturation assay. Results ECL exerted anti-inflammatory activities in acute (84% of inhibition, 2 mg/ear) and chronic models (62.71%, at 100 mg/kg). ECL showed antitumor activity at 200 mg/kg and 300 mg/kg, reducing tumor volume by 30 and 40%, respectively. ECL (9.5 μg/mL) induced in vitro apoptosis in CT26 cells by 29.1% (48 h of treatment) and 93.9% (72 h of treatment). ECL (10 μg/ml) decreased levels of NO (53.7%), pro-inflammatory cytokines IL-6 (44.9%), IL-1β (71.9%), and TNF-α (40.1%), but increased the production of the anti-inflammatory cytokine IL-10 (44%). The diterpenes DEOX, ICT, and DAM decreased levels of NO (38.34, 47.63, 67.15%), IL-6 (57.84, 60.45, 44.26%), and TNF-α (38.90, 31.30, 32.83%), respectively. ECL showed in vitro antiarthritic activity (IC50 = 482.65 μg/mL). Conclusions ECL exhibited anti-inflammatory and anti-tumor activities. Furthermore, the diterpenes DEOX, DAM, and ICT showed anti-inflammatory activity by reducing levels of NO, TNF-α, and IL-6.

A Review on the Ethnopharmacology and Phytochemistry of the Neotropical Sages (Salvia Subgenus Calosphace; Lamiaceae) Emphasizing Mexican Species

“…Carrageenan-induced edema assay was also applied to corroborate the anti-inflammatory properties of the tilifodiolide isolated from S. tiliifolia ( González-Chávez et al, 2018 ) and the ethyl acetate extract containing amarisolide A in higher concentration vs. other extracts of the same Salvia species ( Calzada et al, 2015 ; Fernando et al, 2021 ). To corroborate their anti-inflammatory properties the chloroform and dichloromethane extracts from the aerial parts of S. ballotiflora ( Campos-Xolalpa et al, 2021 ) and S. connivens ( González-Chávez et al, 2017 ), respectively, were explored in the TPA-induced ear edema ( Supplementary Table S2 ).…”

“…Cytotoxic activity was also reported for cariocal isolated from the roots of S. anastomosans ( Esquivel et al, 2005 ). From the chloroform extract of the aerial parts of S. ballotiflora antitumoral and cytotoxicity activities were described ( Campos-Xolalpa et al, 2017 ; Campos-Xolalpa et al, 2021 ), in part due to the presence of 7,20-dihydroanastomosine, 7α-acetoxy-6,7-dihydroicetexone, and anastomosine ( Esquivel et al, 2017 ), as well as 19-deoxyisoicetexone ( Campos-Xolalpa et al, 2017 ). From the roots of S. buchananii it was isolated hyptadienic and salvibuchanic acids ( Beladjila et al, 2018b ), and tilifolidione from S. semiatrata ( Esquivel et al, 2005 ).…”

“…Some of the Mexican species are well known due to their documented nutritional properties (i.e., S. hispanica L.; Cahill, 2003 ; Mohd Ali et al, 2012 ; Ullah et al, 2016 ) or for their psychoactive properties that are of pharmacological interest due to their antinociceptive effects (i.e., Salvia divinorum Epling and Jativa; Jenks et al, 2011 ; Tlacomulco-Flores et al, 2020 ). The most commonly reported bioactive constituents within the subgenus have been characterized as diterpenoids—abietanes and clerodanes—( Bautista et al, 2016 ; Jiang et al, 2016 ; Bautista et al, 2017 ; Esquivel et al, 2017 ; Campos-Xolalpa et al, 2021 ).…”

Dual quinoline-hybrid compounds with antimalarial activity against Plasmodium falciparum parasites

“…LPS is an endotoxin of Gram-negative bacteria that is often used in research to elicit inflammation, and the administration of LPS is known to cause elevation of the IL-1b levels in different systems. 75,76 IL-1b is a potent pro-inflammatory cytokine that is implicated in several inflammation-related diseases, including malaria and other infections. 77,78 This pro-inflammatory cytokine is synthesized and secreted by many cells, such as macrophages, fibroblasts, B lymphocytes and natural killer cells, 79 and acts in a wide range of biological effects.…”

Acyclic Diterpene Phytol from Hemp Seed Oil (Cannabis sativa L.) Exerts Anti-Inflammatory Activity on Primary Human Monocytes-Macrophages

“…Previous data report many therapeutic activities of phytol against mycobacteria and as an anticonvulsant, antispasmodic, or antitumoral agent [ 15 , 16 , 17 ]. Although some data point to the promising anti-inflammatory activity of diterpenes [ 14 , 18 , 19 , 20 , 21 ], little is known about the bioactivity of phytol [ 22 ]. In addition, although it is a major component of the unsaponifiable fraction of HSO, the biological activity in primary human monocytes of isolated HSO phytol has not been studied to date.…”