# Immunoregulatory effects of Choerospondias axillaris (Roxb.) B.L.Burtt & A.W.Hill fruit extract in mice with insights on in vitro mechanism

**Authors:** Ravi Gautam, Anju Maharjan, JaeHee Lee, SuJeong Yang, JiHun Jo, Manju Acharya, DaEun Lee, Narayan Prasad Ghimire, Saroj Lamichhane, ByungSun Min, ChangYul Kim, HyoungAh Kim, Yong Heo

PMC · DOI: 10.1186/s42826-026-00267-9 · Laboratory Animal Research · 2026-03-19

## TL;DR

This study shows that Lapsi fruit extract can boost immunity and reduce inflammation in mice, suggesting it may be useful as an immunomodulatory agent.

## Contribution

The study is the first to demonstrate the immunoregulatory effects of Lapsi fruit extract in vivo and in vitro, including its impact on immune suppression and inflammation.

## Key findings

- Lapsi extract increased IgG2a/IgG1 ratio and reduced IgE and IgG1 levels in mice.
- The extract reversed cyclophosphamide-induced immunosuppression by enhancing immune cell counts and cytokine levels.
- In cell cultures, the extract reduced inflammation markers like nitric oxide and pro-inflammatory cytokines.

## Abstract

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.

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.

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.

The online version contains supplementary material available at 10.1186/s42826-026-00267-9.

## Linked entities

- **Proteins:** TNF (tumor necrosis factor), IL17A (interleukin 17A), Igg-2a (gamma-2a immunoglobulin heavy chain), Ighg1 (immunoglobulin heavy constant gamma 1 (G1m marker)), IGHE (immunoglobulin heavy constant epsilon), CD79A (CD79a molecule), IFNG (interferon gamma), IL4 (interleukin 4), IL6 (interleukin 6), IL1B (interleukin 1 beta)
- **Chemicals:** cyclophosphamide (PubChem CID 2907), nitric oxide (PubChem CID 145068), prostaglandin E2 (PubChem CID 5280360)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Cd3e (CD3 antigen, epsilon polypeptide) [NCBI Gene 12501] {aka CD3, CD3epsilon, T3e}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, CD3E (CD3 epsilon subunit of T-cell receptor complex) [NCBI Gene 916] {aka CD3epsilon, IMD18, T3E, TCRE}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Cd4 (CD4 antigen) [NCBI Gene 12504] {aka L3T4, Ly-4}, Cxcl15 (C-X-C motif chemokine ligand 15) [NCBI Gene 20309] {aka Il8, Scyb15, lungkine, weche}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Ncr1 (natural cytotoxicity triggering receptor 1) [NCBI Gene 17086] {aka Cd335, Ly94, NKp46}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, Ptprc (protein tyrosine phosphatase receptor type C) [NCBI Gene 19264] {aka B220, CD45R, Cd45, L-CA, Ly-5, Lyt-4}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il2 (interleukin 2) [NCBI Gene 16183] {aka Il-2}, Apc (APC, WNT signaling pathway regulator) [NCBI Gene 11789] {aka CC1, Min, mAPC}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Ighv1-9 (immunoglobulin heavy variable 1-9) [NCBI Gene 668478] {aka Gm16697, Igg2a}, Ighg1 (immunoglobulin heavy constant gamma 1 (G1m marker)) [NCBI Gene 16017] {aka IgG1, Igh-4, VH7183}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Jun (Jun proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 16476] {aka AP-1, Junc, c-jun}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Itga2 (integrin alpha 2) [NCBI Gene 16398] {aka CD49B, DX5, GPIa}, Nfkbia (nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, alpha) [NCBI Gene 18035] {aka Nfkbi}, pma (peroneal muscular atrophy) [NCBI Gene 18849], Actb (actin, beta) [NCBI Gene 11461] {aka Actx, E430023M04Rik, beta-actin}
- **Diseases:** restlessness (MESH:D011595), sepsis (MESH:D018805), insomnia (MESH:D007319), atopic dermatitis (MESH:D003876), cancer (MESH:D009369), TDM (MESH:D055501), viral (MESH:D014777), arrhythmic (OMIM:212500), autoimmune diseases (MESH:D001327), respiratory allergies (MESH:D012131), allergic (MESH:D004342), arrhythmia (MESH:D001145), Inflammatory (MESH:D007249), hypoxic (MESH:D002534), myocardium impairment (MESH:D017682), neurological problems (MESH:D009461), asthma (MESH:D001249), immune dysregulation (OMIM:614878), cardiac-related disorders (MESH:D006331), carcinogenesis (MESH:D063646), dysregulation (MESH:D021081), septic shock (MESH:D012772), infections (MESH:D007239), myocardial (MESH:D009202), ischemia (MESH:D007511), rheumatoid arthritis (MESH:D001172), cytotoxic (MESH:D064420), cardiovascular conditions (MESH:D002318), arthritis (MESH:D001168)
- **Chemicals:** aconitine (MESH:D000157), penicillin (MESH:D010406), DMSO (MESH:D004121), sodium fluoride (MESH:D012969), amino acids (MESH:D000596), octacosanol (MESH:C044309), ROS (MESH:D017382), 2-mercaptoethanol (MESH:D008623), procyanidins (MESH:D044945), water (MESH:D014867), saline (MESH:D012965), quercetin (MESH:D011794), daucosterol (MESH:C011015), PGE2 (MESH:D015232), CP (MESH:D003520), Flavonoid (MESH:D005419), polyphenol (MESH:D059808), flavones (MESH:D047309), ATP (MESH:D000255), LPS (MESH:D008070), vitamin C (MESH:D001205), sodium bicarbonate (MESH:D017693), Tween 80 (MESH:D011136), CO2 (MESH:D002245), saccharides (MESH:D002241), polystyrene (MESH:D011137), anthocyanidins (MESH:D000872), ethanol (MESH:D000431), phenylmethylsulfonyl fluoride (MESH:D010664), syringaldehyde (MESH:C069665), PVDF (MESH:C024865), curcumin (MESH:D003474), vanillic acid (MESH:D014641), streptomycin (MESH:D013307), H2DCF-DA (MESH:C110400), citric acid (MESH:D019343), Lapsi (-), linoleic acid (MESH:D019787), gallic acid (MESH:D005707), NO (MESH:D009569), DNCB (MESH:D004137), pectin (MESH:D010368), Phorbol 12-myristate-13-acetate (MESH:D013755), essential amino acids (MESH:D000601), polysaccharide (MESH:D011134), dihydroquercetin (MESH:C003377), Griess reagent (MESH:C095000), adriamycin (MESH:D004317), SDS (MESH:D012967), stearic acid (MESH:C031183), catechin (MESH:D002392), protocatechuic acid (MESH:C009091), FITC (MESH:D016650), CCK-8 (MESH:D012844), 3,3-di-o-methylellagic acid (MESH:C050401)
- **Species:** Chionanthus axillaris (species) [taxon 1382063], Rattus norvegicus (brown rat, species) [taxon 10116], Choerospondias axillaris (species) [taxon 289701], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006), TDM — Labeo rohita (Indian major carp), Spontaneously immortalized cell line (CVCL_A8VR)

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13001281/full.md

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Source: https://tomesphere.com/paper/PMC13001281