## 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  
Some other in vivo studies share a common focus on exploring the anti-inflammatory properties of lotus plant extracts, albeit with variations in the specific conditions studied, bioactive compounds identified, methodologies employed and outcome measures assessed. [PERSON] et al., [PERSON] et al. and [PERSON] et al. investigated the anti-inflammatory effects of extracts derived from _N. nucifera_ leaves, namely lotus leaf flavonoid extract (LLFE) [23], _N. nucifera_ leaves extract (NLE) [54] and _N. nucifera Gaertn._ leaves [55], respectively, while [PERSON] and [PERSON] examined the Lotus Plumule Polysaccharide (LPDS) [56]. These studies all highlight the presence of bioactive compounds in lotus plant extracts, such as flavonoids, phenolic acids, and polysaccharides, which are credited for their anti-inflammatory properties. However, the specific bioactive components differ among the studies. For instance, LLFE contains Baicalein, Kaempferol, Kaempferol, Quercetin, Isorhamnetin, Hyperoside, Lespenephryl and Rutin [23]. NLE comprises phenolic acids and flavonoids, with major polyphenols like gallic acid, protocatechuic acid, catechin, gallocatechin gallate, caffeic acid, epicatechin, rutin, quercetin and naringenin [54]. _N. nucifera Gaertn._ leaves extract contains Sitosterol, Pronuciferine, Nuciferine, Nelumboside, Quercetin and Kaempferol [55], and LPDS consists of polysaccharides [56]. All these studies utilised in vivo mouse models to evaluate the anti-inflammatory effects of lotus plant extracts in different inflammatory conditions, including aging-induced inflammation [23], alcoholic steatohepatitis [54], atherosclerosis [55] and type 1 diabetes [56]. The methodologies employed vary across the studies, encompassing analyses of mRNA expression levels of pro-inflammatory cytokines [23], immunohistochemistry and Western blot analysis of liver tissue sections [54], molecular docking and network pharmacology [55] and cytokine gene expression analysis in various organs [56]. Despite these methodological differences, a consistent trend is observed in all studies, indicating a reduction in pro-inflammatory cytokines like TNF-\(\alpha\), IL-6, IL-1\(\beta\) and interferon-\(\gamma\) (IFN-\(\gamma\)) following treatment with lotus plant extracts, suggesting their potential anti-inflammatory efficacy. Additionally, [PERSON] et al. demonstrated an increase in the levels of anti-inflammatory cytokines IL-10 and IL-12, crucial for immune response modulation and inflammation suppression [23], while a study conducted by [PERSON] and [PERSON] showed reduced spleen size and altered cytokine gene expression in the liver, indicating protection against spontaneous inflammation in non-obese diabetic (NOD) mice and the ability to balance pro- and anti-inflammatory responses in type 1 diabetes [56]. Another clinical study by [PERSON] et al. showed that _N. uncifera_ extracts using ethanol as a solvent inhibited the production of cytokine genes, slowed cell cycle progression and proliferated human peripheral blood mononuclear cells. Blood from 15 healthy subjects was taken and analyzed with lymphoprolliferation test, cell cycle analysis and polymerase chain reaction (PCR). The results showed that the extract suppressed proliferation in peripheral blood mononuclear cells (PBMC) activated by phytohaemagglutinin (PHA). It also reduced tissue inflammation-in part by inhibiting PBMC proliferation [57]. [PERSON] et al. explored the anti-inflammatory effects of betulinic acid, a steroidal triterpen compound derived from the _N. uncifera_ rhizomes, in male albino Wistar rat models with paw edema induced by carrageenanin and serotonin. It aimed to assess the anti-inflammatory potential of this bioactive compound and compare its effectiveness with standard drugs like phenylbutazone and dexamethasoneone.