Studies On Chemical Constituents Of The Gum Resin Of Boswellia Carterii

Ulcerative colitis (UC) is a chronic inflammatory bowel disease. It is treated as an autoimmune disease and seriously affects the quality of patients’life. UC is always listed as a nasty and complicated disease by WHO. At present, the drugs for treating UC are very deficient and most of them usually have serious side effects. Thus developing new and effective anti-UC compounds from natural resources is of great significance for drug discovery.Olibanum (Frankincense), which is the gum-resin exuded via_incision from the bark of the Boswellia carterii Birdw or Boswellia bhaw-dajiana Birdw, is a famous crude drug in traditional Chinese medicine (TCM). It has been used to treat rheumatic arthralgia, chest obstruction, dysmenorrheal, and amenorrhea, and so forth for a long time in the history of China. On the other hand, according to the definition of modern pharmacology, the extract of frankincense and its constituents possess analgesic, anti-inflammatory, sedative, cytotoxic, and antioxidant bioactivities. However, to the best of our knowledge, there has been no report on anti-UC activity of Frankincense. In order to look for more novel and bioactive natural compounds, the chemical constituents of the gum resin of Boswellia carterii was studied in this paper.Taking advantage of a variety of chromatographic techniques including Silica gel column chromatography (CC), Silica gel H CC, silica gel H vacuum CC, RPC18 vacuum CC, and preparative RP-HPLC,60 compounds were isolated from the CH2Cl2 and EtOAc fractions of ethanol extract of the gum resin of Boswellia carterii. Names and structures of these compounds are listed in Table 1 and Figure 1. The structures were determined by in-depth spectroscopic examination, mainly including multiple 1D- and 2D-NMR and HRESIMS experiments and analyses. Compounds 1-26 were new compounds. According to structural patterns, the isolated compounds were classified into triterpenes (19-21,27-45), cembranoid diterpenes (1-18,46-51), prenylaromandendrane diterpenes (22-25,52-56), prenylmaaliane diterpenes (26), and others (57-60).The determination of absolute configurations are the important part of studying the structures of cembranoid diterpenes (1-18). In this paper, the structures and absolute configurations of 1-4 were unequivocally resolved using single-crystal X-ray diffraction analysis with Cu Kα radiation. By careful analysis of crystal diffraction diagram of these compounds, the skeleton information of this class of compound could be obtained, which provides reference for the structural determination of cembranoid diterpenes in this study. In addition, to the best of our knowledge, diterpene (26) was the first report on prenylmaalianoids.Based on the anti-inflammatory effect of frankincense in clinic, the potential activity of anti-Ulcerative colitis (UC) of all of the isolated new compounds were evaluated in an in vitro x-box-binding protein 1 (xbpl) transcriptional activity assay using dual luciferase reporter detection; xbpl is a transcription factor associated with the occurrence, exacerbation, and potential treatment of UC. According to the findings, all the new compounds, especially cembranoids can activate the transcription of xbpl, Among them, compounds 1,5-7 have significant activity and their activation rates were 1.47,1.58,2.4, and 1.9 compared with the pGL3-basic vector control at a concentration of 10 μM. In order to futher confirmed their activities, the half maximal effect concentration (EC50) of 1,5-7 were determined and they were 0.34 μM,1.14μM,0.88 μM, and 0.42 μM,_respectively. To the best of our knowledge, this is the first report on Xbpl transcriptional activity of cembranoid.