Laboratory of Veterinary Physiology, Department of Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, 582 Bunkyodai-Midorimachi, Ebetsu, Hokkaido, 069-8501, Japan.
Laboratory of Medicinal Resources, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi, 464-8650, Japan.
BMC Complement Altern Med. 2018 May 2;18(1):138. doi: 10.1186/s12906-018-2198-5.
Brazilian green propolis is produced by mixing secretions from Africanized honey bees with exudate, mainly from Baccharis dracunculifolia. Brazilian propolis is especially rich in flavonoids and cinammic acid derivatives, and it has been widely used in folk medicine owing to its anti-inflammatory, anti-viral, tumoricidal, and analgesic effects. Moreover, it is applied to prevent metabolic disorders, such as type 2 diabetes and arteriosclerosis. Previously, we demonstrated that propolis ethanol extract ameliorated type 2 diabetes in a mouse model through the resolution of adipose tissue inflammation. The aims of this study were to identify the immunosuppressive cells directly elicited by propolis extract and to evaluate the flavonoids that induce such cells.
Ethanol extract of Brazilian propolis (PEE; 100 mg/kg i.p., twice a week) was injected into lean or high fat-fed obese C57BL/6 mice or C57BL/6 ob/ob mice for one month. Subsequently, immune cells in visceral adipose tissue and the peritoneal cavity were monitored using FACS analysis. Isolated macrophages and the macrophage-like cell line J774.1 were treated with PEE and its constituent components, and the expression of immune suppressive myeloid markers were evaluated. Finally, we injected one of the identified compounds, kaempferol, into C57BL/6 mice and performed FACS analysis on the adipose tissue.
Intraperitoneal treatment of PEE induces CD11b, Gr-1 myeloid-derived suppressor cells (MDSCs) in visceral adipose tissue and the peritoneal cavity of lean and obese mice. PEE directly stimulates cultured M1 macrophages to transdifferentiate into MDSCs. Among twelve compounds isolated from PEE, kaempferol has an exclusive effect on MDSCs induction in vitro. Accordingly, intraperitoneal injection of kaempferol causes accumulation of MDSCs in the visceral adipose tissue of mice.
Brazilian PEE and its compound kaempferol strongly induce MDSCs in visceral adipose tissue at a relatively early phase of inflammation. Given the strong anti-inflammatory action of MDSCs, the induction of MDSCs by PEE and kaempferol is expected to be useful for anti-diabetic and anti-inflammatory therapies.
巴西绿蜂胶是由非洲化蜜蜂的分泌物与渗出物（主要来自 Baccharis dracunculifolia）混合而成。巴西蜂胶富含类黄酮和肉桂酸衍生物，由于具有抗炎、抗病毒、抗肿瘤和镇痛作用，已在民间医学中广泛应用。此外，它还用于预防代谢紊乱，如 2 型糖尿病和动脉硬化。先前，我们证明蜂胶乙醇提取物通过缓解脂肪组织炎症改善了 2 型糖尿病小鼠模型。本研究的目的是鉴定蜂胶提取物直接诱导的免疫抑制细胞，并评估诱导此类细胞的类黄酮。
将巴西蜂胶乙醇提取物（PEE；100mg/kg，腹腔内注射，每周两次）注射到瘦或高脂肪喂养的肥胖 C57BL/6 小鼠或 C57BL/6 ob/ob 小鼠中一个月。随后，使用 FACS 分析监测内脏脂肪组织和腹腔中的免疫细胞。用 PEE 及其成分处理分离的巨噬细胞和巨噬细胞样细胞系 J774.1，并评估免疫抑制性髓样标记物的表达。最后，我们将鉴定出的一种化合物，山奈酚，注射到 C57BL/6 小鼠中，并对脂肪组织进行 FACS 分析。
PEE 腹腔内治疗可诱导瘦鼠和肥胖鼠内脏脂肪组织和腹腔中 CD11b、Gr-1 髓样来源抑制细胞（MDSCs）。PEE 直接刺激培养的 M1 巨噬细胞向 MDSC 转化。从 PEE 中分离出的十二种化合物中，山奈酚对 MDSC 的诱导具有独特的作用。因此，腹腔内注射山奈酚可导致小鼠内脏脂肪组织中 MDSC 的积累。
巴西 PEE 及其化合物山奈酚在炎症的早期阶段强烈诱导内脏脂肪组织中的 MDSC。鉴于 MDSC 的强烈抗炎作用，PEE 和山奈酚诱导 MDSC 的作用有望用于抗糖尿病和抗炎治疗。
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