Background: Lapsi (Choerospondias axillaris), a plant native to Nepal, has been traditionally used in Asian countries to treat cardiovascular conditions. However, its effects on immune regulatory function remain largely unexplored.This study aimed to in vivo evaluate the immunoregulatory properties of Lapsi fruit extract in mice on immunotoxic responses with analysis on in vitro mechanism for immune suppression, oxidative stress, and inflammatory response.Male Balb/c mice were intragastrically administered various doses of the extract for 21 days. In some mice, immune suppression was induced with cyclophosphamide, and subsequent immune recovery was assessed. In addition, RAW264.7 cells and THP-1-derived macrophages were treated in vitro with lipopolysaccharide and different concentrations of the extract. Results: Administration of extract increased the IgG2a/IgG1 ratio while reducing serum IgE and IgG1 level compared with control mice. Tumor necrosis factor (TNF)-α and interleukin (IL)-17 levels were lower in splenic culture supernatants of mice administered extract. Lapsi extract also effectively reversed cyclophosphamide (CP)-induced immunosuppression by enhancing serum levels of IgA and IgG2a, of interferon-γ and interleukin (IL)-4 secreted by splenic T cells, and of IgG1 and IgG2a secreted by B cells, as well as by increasing immune cell counts. In cell cultures, the extract decreased the levels of inflammation markers, including nitric oxide, reactive oxygen species, prostaglandin E2, and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). Mechanistic analysis showed that Lapsi extract modulated the NF-κB p65, MAPK, and inflammasome pathways. Conclusions Lapsi extract may act as both an immunostimulatory and anti-inflammatory agent, indicating its potential as a candidate immunomodulatory activity under polyclonal and CP-suppressed conditions; however, further disease-specific studies, along with isolation and characterization of active phytochemicals, are warranted to evaluate its therapeutic applicability.

Background: Atopic dermatitis (AD) is a biphasic type of skin inflammation characterized by a predominance of type-2 ­(TH2) and type-1 ­(TH1) helper T cell-biased immune responses at the acute and persistent chronic phases, respectively. The present study was aimed to evaluate the efficacy of Artemisia dubia folium extract (ADFE) on ADlike skin lesions through developing a murine model for acute and chronic stages of AD. To induce acute phase AD, the dorsal skin of BALB/c mice was sensitized twice a week with 1% 2, 4-dinitrochlorobenzene (DNCB), followed by challenge (twice) in the following week with 0.2% DNCB. To induce persistent chronic AD, some mice were challenged twice a week for 4 more weeks. After the second challenge, the dorsal skin was exposed to 3% ADFE (five times per week) for 2 weeks (acute phase) or 4 weeks (persistent chronic phase). Results: The paradigm of ­TH2 or  ­TH1 predominance at the acute and chronic phase, respectively, was observed in this mouse model. During the acute phase, we observed an increased IL-4/IFN-γ ratio in splenic culture supernatants,an increased IgG1/IgG2a ratio in serum, and elevated serum IgE levels; however, the skew toward ­TH2 responses was diminished during the chronic stage. Compared with vehicle controls, ADFE reduced the IL-4/IFN-γ and IgG1/ IgG2a ratios in acute AD, but both ratios increased during the chronic stage. Conclusions Our results suggest that ADFE concomitantly suppresses the ­TH2 predominant response in acute AD, as well as the ­TH1 predominant response in chronic AD. Thus, ADFE is a candidate therapeutic for AD.