Houttuynia cordata Thunb. Essential Oil Inhibits Diffuse Large B-cell lymphoma Growth

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) with high clinical heterogeneity and poor prognosis. Therapeutic drugs that can effectively improve the survival rate of DLBCL patients are lacking. Houttuynia cordata Thunb. is a well-known Asian medicinal and edible plant with anti-inflammatory and anti-tumor activities. This study investigated the potential therapeutic benefits of Houttuynia cordata Thunb. Essential Oil (HEO) on DLBCL. We found that HEO inhibited the proliferation of SUDHL-4 cells, induced apoptosis and cell cycle arrest at G0/G1 phase in a time and concentration-dependent manner. Moreover, intraperitoneal administration of HEO (70, 150, and 230 mg/kg) dose-dependently inhibited tumor growth of DLBCL in an athymic nude mouse xenograft model, while no significant changes in body weight were observed, indicating no obvious toxicity. Network pharmacology analysis indicated that HEO mainly regulated protein phosphorylation and PI3K/Akt signaling pathway. Phospho-specific protein microarray results also showed that HEO regulated the phosphorylation of PI3K/Akt signaling pathway. Further investigation confirmed that HEO significantly inhibited the protein expression of p-PI3K and p-Akt. In addition, HEO decreased the protein expression of B-cell lymphoma 2 (Bcl-2) and increased the protein expression of Bcl-2-associated X (Bax) and caspase-3. Compound-target docking results displayed that bornyl acetate (the main components of HEO), caryophyllene oxide and terpineol had strong binding interactions with the active sites of PI3K and Akt, indicating they contribute to the therapeutic effect. These results demonstrated that HEO exerts anti-tumor effects in DLBCL via suppressing PI3K/Akt signaling pathway, indicating HEO may be a potential inhibitor of PI3K/Akt signaling pathway for the treatment of DLBCL.