# _Holarrhena pubescens_ Wall. ex G. Don Extracts Inhibit
###### Abstract  
_Holarrhena pubescens_ Wall. ex G. Don (_H. pubescens_), belonging to the _Apocynacacae_ family, is distributed in deciduous forests of the tropical Himalayas. _H. pubescens_ is an important traditional medicinal plant, especially its seeds and barks. Therefore, we assessed the antioxidant capacity of _H. pubescens_ extracts in Lipopolysaccharide-induced dendritic cells (DCs) for sepsis treatment. Our results indicated that _H. pubescens_ extracts with different doses (25 ug/mL, 50 ug/mL, 100 ug/mL) reduced the reactive oxygen species (ROS) level, and weakened the nitric oxide synthases (NOS) activity and nitric oxide (NO) level in LPS (100 ng/mL)-irritated DCs. In addition, _H. pubescens_ extracts decreased the oxidized glutathione (GSSG) production but increased the reduced glutathione (GSH) production, thereby preserving the cellular reductive status owing to the raised GSH/GSSG ratio. Furthermore, _H. pubescens_ extracts strengthened the antioxidant enzymes activity in LPS-induced DCs, such as glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). Finally, we found that _H. pubescens_ extracts significantly improved the expression of the nuclear factor erythroid 2-related factor 2 (Nrf2) and the heme oxygenase 1 (HO-1) in LPS-irritated DCs. These results indicated that _H. pubescens_ extracts suppressed the LPS-irritated oxidative stress in DCs via Nrf2/HO-1 signaling pathway, providing a potential strategy for sepsis therapy. Keywords:herbal medicines; _H. pubescens_; oxidative stress; dendritic cells +
Footnote †: journal: Medical  
the redox homeostasis is destroyed and excess ROS and RNS is produced, in turn enhancing dysfunction caused by sepsis, leading to a vicious cycle [13; 14]. In addition, previous studies have reported that many sepsis patients exhibit features of ROS overproduction and antioxidant system dysfunction, implying that oxidative stress is closely related to sepsis [15; 16]. Moreover, the occurrence and development of many illnesses are related to oxidative stress, including traumatic brain injury (TBI), osteoporosis, and atherosclerosis [17; 18; 19]. Some studies have found that lipopolysaccharide (LPS) can destroy the immune function of DCs during the development of sepsis [20; 21]. ROS, acting as a mediator of oxidative stress, can also destroy the immunomodulatory function of DCs. For instance, ROS-triggered endoplasmic reticulum stress disrupts the antitumor immune function of DCs in ovarian cancer [22]. This may be linked to the immune dysfunction of DCs caused by oxidative stress. Our previous studies indicated that the inhibition of oxidative stress protected LPS-stimulated DCs from immunosuppression and reduced inflammatory reaction in an LPS-induced sepsis murine model [23; 24; 25]. Therefore, a DC-targeting strategy could be a significant and potential sepsis treatment. Herbal medicines play a vital role in global medical development. In developing Asian countries, 70-80% of rural people conduct primary health care mainly using traditional medicine [26]. _Holarhena pubescens_ Wall. ex G. Don (_H. pubescens_), belonging to the _Apocyanoaceae_ family, is an important natural medical material. _H. pubescens_ is usually distributed in the tropics and subtropics of Asia, especially in the deciduous forests of the tropical Himalayas, at altitudes ranging from 900 to 1250 m [27]. _H. pubescens_ is usually used as a conventional medicine for parasitosis, such as malaria, amoebic dysentery, and intestinal helminthiasis treatment, further studies found that _H. pubescens_ has multiple functions, including anti-microbial, anti-inflammatory, analgesic, anti-amnesic, and neuroprotective functions [28]. In addition, _H. pubescens_ can be developed as a potential drug against diabetes and various enteric skin diseases. Each part of _H. pubescens_ has different functions, for example, its barks and seeds are mostly used to treat diarrhea and dysentery, its roots can resist malaria, and its leaves can control stomachache and vomiting [29; 30; 31; 32].