Gastric Ulcer Healing Property of Bryophyllum pinnatum Leaf Extract in Chronic Model In Vivo and Gastroprotective Activity of Its Major Flavonoid

Abstract

Gastric ulcer is a common disease that develops complications such as hemorrhages and perforations when not properly treated. Extended use of drugs in the treatment of this pathology can provoke many adverse effects. Therefore, finding medicinal plants with gastroprotective and mucosal healing properties has gained increasing interest. Bryophyllum pinnatum (Crassulaceae), popularly known in Brazil as “saião” or “coirama,” has been used to treat inflammatory disorders. It is rich in flavonoids, and quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside-Bp1 is its major compound. In this study, we aimed to investigate ulcer healing properties of B. pinnatum against an acetic acid–induced chronic ulcer model and the gastroprotective activity of Bp1 against gastric lesions induced by ethanol and indomethacin. Ultrafast liquid chromatography was used to quantify the main compounds (mg/g of the extract)—quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (33.12 ± 0.056), kaempferol 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (3.98 ± 0.049), and quercetin 3-O-α-L-rhamnopyranoside (4.26 ± 0.022) and showed good linearity, specificity, selectivity, precision, robustness, and accuracy. In vivo studies showed that treatment with the extract at 250 and 500 mg/kg stimulated the healing process in the gastric mucosa with significant ulceration index reduction, followed by improvement in the antioxidant defense system [increased glutathione (GSH) levels, decreased superoxide dismutase upregulation, and malondialdehyde (MDA) levels]. Moreover, the extract decreased interleukin-1β and tumor necrosis factor-a levels and myeloperoxidase (MPO) activity, increased interleukin 10 levels, showed a cytoprotective effect in histological analyzes and also downregulated the expression of cyclooxygenase-2 and NF-κB (p65). The pretreatment with Bp1 at a dose of 5 mg/kg reduced gastric lesions in the ethanol and indomethacin models, increased GSH, and decreased MDA levels. In addition, the pretreatment decreased MPO activity, interleukin-1β and tumor necrosis factor-α levels, while also showing a cytoprotective effect in histological analyzes. Our study suggests that treatment with B. pinnatum extract showed a higher inhibition percentage than pretreatment with the Bp1. This might in turn suggest that Bp1 has gastroprotective activity, but other compounds can act synergistically, potentiating its effect. We conclude that B. pinnatum leaf extract could be a new source of raw material rich in phenolic compounds to be applied in food or medicine.

Gel formulated with Bryophyllum pinnatum leaf extract promotes skin wound healing in vivo by increasing VEGF expression: A novel potential active ingredient for pharmaceuticals

“…In the literature, it is described that the main phenolic compounds identified in the leaves of the species B. pinnatum are the glycosylated flavonoids derived from quercetin, kaempferol, and luteolin ( Muzitano, 2006 ; Cruz et al, 2008 ; El Abdellaoui et al, 2010 ; Tatsimo et al, 2012 ; Darmawan, 2013 ; Aoki et al, 2014 ; Chibli et al, 2014 ; Fernandes et al, 2016 ; De Araújo et al, 2018 ; Dos Santos Nasimento et al, 2018 ; Fernandes et al, 2019 ; Andrade et al, 2020 ; De Araújo et al, 2021 ). Furthermore, the content of three flavonoids of B. pinnatum aqueous leaf extract, quercetin 3- O - α -L-arabinopyranosyl-(1→2)- O - α -L-rhamnopyranoside (Bp1), kaempferol 3- O - α -L-arabinopyranoside (1→2)- O - α -L-rhamnopyranoside (Bp2), and quercetin 3- O - α -L-rhamnopyranoside (Bp3) was previously determined, in which Bp1 was the major compound identified ( De Araújo et al, 2021 ). According to previous studies ( Dos Santos Nascimento et al, 2018 ; Coutinho et al, 2021 ), the results of this analysis confirmed that Bp1 is considered an analytical marker of this species.…”

“…In the literature, it is described that the main phenolic compounds identified in the leaves of the species B. pinnatum are the glycosylated flavonoids derived from quercetin, kaempferol, and luteolin (Muzitano, 2006;Cruz et al, 2008;El Abdellaoui et al, 2010;Tatsimo et al, 2012;Darmawan, 2013;Aoki et al, 2014;Chibli et al, 2014;Fernandes et al, 2016;De Araújo et al, 2018;Dos Santos Nasimento et al, 2018;Fernandes et al, 2019;Andrade et al, 2020;De Araújo et al, 2021). Araújo et al, 2021).…”

“…In a review article published in 2019 ( Fernandes et al, 2019 ), our research group gathered information about the traditional use of their leaves for treating the healing processes of skin and stomach wounds. A state-of-science review of this species revealed an extract with healing properties for treating ulcers ( De Araújo et al, 2021 ), and a topical gel containing an extract showed potential to treat skin wounds ( Coutinho et al, 2021 ); and another formulation in gel containing an extract had acute anti-inflammatory potential ( De Araújo et al, 2019 ) in in vivo models. Specifically, this last study conducted by our research group encouraged us to follow a deep investigation to prove the wound healing efficacy of gel containing B. pinnatum leaf extract and understand its mechanism of action using the experimental model of induction of skin wounds in rats.…”

Ulcero-Protective Potential of Ethyl Acetate Fractions of Persea americana Seed and Bryophyllum pinnatum Leaf Binary Combinations in Indomethacin Induced Gastric Ulcer

“…Brena et al [36], reported that avocado seeds may prevent gastric mucosal injury and oxidative stress induced by indomethacin. Also, the works of Sharma et al [38], Amadi et al [39]; De Araújo et al [40] reported gastric protecting property of different solvent extracts of B. pinnatum. In our study, the ulceroprotective effect of the binary combinations was significantly higher when compared to the single plant fractions.…”

Phenolic-rich extract of Nopalea cochenillifera attenuates gastric lesions induced in experimental models through inhibiting oxidative stress, modulating inflammatory markers and a cytoprotective effect

“…64 According to Zhao et al 65 and Liu et al, 66 flavonoids play a key role in the gastroprotective mechanism by maintaining the physiological pH of the gastric juice. In a study carried out by our research group, De Araújo et al 67 evaluated the gastroprotective effect of flavonoid quercetin 3-O-α-L-arabinopyranosyl-(1 → 2)-O-α-L-rhamnopyranoside, isolated from the species Bryophyllum pinnatum, against ethanol and indomethacininduced gastric lesion models. In this study, it was observed that the pre-treatment with this flavonoid showed gastroprotective activity, significantly improving parameters of oxidative stress and inflammation in gastric tissue.…”