## 1 Introduction  
Bone is a biological tissue able to regenerate in case of traumas or degenerative pathologies. After bone injuries, the physiopathology of the tissue healing follows different stages. The first key-step is the chemotaxis of immune cells from the bloodstream, as they will promote the activation of the inflammatory response to the injury [1]. At the same time, resident and \"sleeping\" mesenchymal stem cells (MSCs) activate and migrate into the injured tissue, from the bone marrow. MSCs effectively start the repairing process [2]. Locally, MSCs will differentiate into chondrocytes and osteoblasts. The healing process continues with the remodeling of the newly formed bone, so restoring the anatomical shape and function [3].  
In healthy people, about 10% of fracture healings may go wrong [4]; on the other hand, the risk of experience a problem in healing is increased 6- to 7-fold for type 1 diabetes patients, and 1.4- to 1.7-fold for people with type 2 diabetes [5]. Moreover, the healing time is typically prolonged in about 87% of diabetics, and the risk of complication, such as delayed union is 3.4-fold higher [6; 7; 8]. Besides, several studies have reported that diabetic patients have an impairment of the MSC osteogenic commitment and osteoblasts function: Both these conditions certainly contribute to worsening the bone healing [9]. It this landscape, the bone healing and repairing may need to be improved with biocompatible and osteoinductive therapies to promote bone regeneration.  
The Yunnan Baiyao (YB) is a well known Chinese herbal medicine, firstly introduced in the healthcare market in 1914 [10]. The main compounds of YB are: Radix Notoginseng (Panax pseudoginseng var. notoginseng ([PERSON] [PERSON]), Borneolum Syntchicum (Cinnamomum camphora (L.) [PERSON]), and Radix Aconiti Kusnezoffii (Aconitum Kusnezoffii Reichb.); however, the exact composition is confidential, because it is one of the two Class-1 protected traditional Chinese Medicines [10; 11]. Nevertheless, some studies tried to characterize the main active principles working in YB, revealing the presence of saponins, terpenids and steroid glycosides [12; 13]. Recently, [PERSON] et al. [11] reported the presence of five terpenoid saponins and eight steroidal saponins in YB powder and capsules that contribute to its therapeutic efficacy. In fact, YB has been reported to have several therapeutic properties in clinical cases reporting severe inflammation or tissue damage.  
Interestingly, the most reported pharmacological effects of YB are related to its hemostatic properties [14]. The anti-inflammatory effect, the ability to improve wound healing, and bone regeneration have also recently been added to this [10; 11]. Despite all these effective properties, there are also limitations mainly related to the scarce information reported in the scientific literature. YB effects have not been well investigated in vitro, and most of the studies on YB are published in Chinese literature, making them difficult to be understood globally [15; 16]. Specifically, the effects of YB on bone regeneration are reported in few papers, and they describe contrasting effects. [PERSON] et al. [17] reported that YB could improve the fractures healing in a rabbit model; on the contrary, [PERSON] et al. [18] indicated that YB does not increase the formation of new bone, after a third molar extraction in humans.  
We aim to give a robust and reliable point of view, taking into consideration the previous literature, about the effects of YB on bone regeneration. In more detail, we will investigate whether YB can induce new bone formation through the differentiation of MSCs towards osteogenic phenotype. Our null hypothesis emphasizes the synergic effect of terpenoid and steroidal saponins on the overall process of bone healing: we assume that such molecular synergy will promote the osteogenic commitment of adipose mesenchymal stem cells, thus improving the timing and the quality of bone healing.