## 3 _Nelumbo nucifera_
### Antioxidant Health Promoting Effect of Nelumbo uncifera Bioactives and Extracts
#### 3.3.2 In Vivo Anti-Inflammatory Health Benefits of _Nelumbo_ nucifera's Bioactives and Extracts
Betulinic acid was administered orally at specified doses to evaluate its impact on inflammation by measuring paw volumes and inflammation rates at different time points. The findings indicated significant anti-inflammatory activity at doses of 50 and 100 mg/kg, showing effects similar to phenylbutazone and dexamethasoneone. The study suggested that betulinic acid may operate through a delayed mechanism akin to glucocorticoids, hinting at a potential interaction with the glucocorticoid receptor [58]. These and other in vivo studies aimed to evaluate and validate the anti-inflammatory effects of _N. uncifera_ plant extracts using animal models (rats [48; 59; 60] or mice [53]) with various plant extract formulations. In two of these studies, rat models were employed to facilitate the in vivo evaluation of the anti-inflammatory activity of plant extracts from different parts of the _N. uncifera_ plant. They utilised the Carrageenanin-induced paw edema model to induce inflammation and assess the anti-inflammatory properties of methanol-extracted lotus seeds (white and red) [59] and ethanol-extracted lotus fruit [60]. Paw volume measurements were taken at various time points post-inflammation induction to evaluate the extent of edema and the effects of the extracts. [PERSON] and [PERSON] also included a COX-2 enzyme inhibition assay to investigate how lotus seeds inhibit the COX-2 enzyme [59]. Both studies reported a significant reduction in paw volume, indicating the anti-inflammatory effects of lotus seed and fruit extracts in response to carrageenanin-induced inflammation. However, the time point at which the maximum reduction in paw edema occurred differed, with [PERSON] and [PERSON] observing it at the third hour after carrageenanin injection [59], and [PERSON] et al., at the fifth hour [60]. Furthermore, the study on lotus seed extracts demonstrated anti-inflammatory properties and significant inhibition in the enzyme assay, with white lotus seed extracts at higher doses showing more pronounced inhibition [59]. While both studies attributed their results to the presence of phytochemical constituents in the plant extracts, specific compounds like flavonoids, saponins and tannins were specifically highlighted in one of the studies [59]. In two additional studies, the anti-inflammatory properties of _N. uncifera_ extracts were assessed in liver inflammation and damage using animal models, with one study involving rats and the other involving mice [53]. The _N. uncifera_ Leaf Extract (NLE) was obtained using distilled water in one study [48], while Lotus Seedpod Extract (LSE) was prepared using hot water in the other [53]. The targeted inflammatory pathways differed between the studies, with the former investigating the impact of NLE on AAF-induced hepatocarcinogenesis [48], while the latter examined the effects of LSE on LPS-inducedhepatic inflammation [53]. In terms of liver damage assessment, [PERSON] et al. aimed to alleviate 2-acetylaminofluorene (AAF)-induced liver damage, inflammation, and oxidative stress [48], while [PERSON] et al. focused on observing changes in hepatic lobular architecture and liver damage induced by LPS [53]. Both studies reported a decrease in pro-inflammatory mediators (IL-6, TNF-\(\alpha\)) following treatment with \(N\). _nucifera_ extracts, indicating their potential anti-inflammatory effects. Furthermore, the results on LPS-induced hepatic inflammation demonstrated a dose-dependent reduction in serum markers of liver damage, improvement in hepatic lobular architecture, reduced secretion of pro-inflammatory mediators and increased levels of antioxidant enzymes [53]. HPLC analysis was conducted in both studies to identify specific phenolic compounds present in the extracts. The compounds identified included gallic acid and catechin in one study [48] and catechin, procyanidin B2, \(p\)-coumaric acid and (-)-epigallocatechin (EGC) in the other [53].