| Objectives:Taking the agarwood broken pieces and traditional pieces as research objects,the differences in the content of alcohol-soluble extracts and agarwood tetraols were discussed.n terms of pharmacodynamics,the differences in pharmacological effects of analgesia,gastrointestinal motility,and anti-gastric ulcer on the pharmacological effects of the two,and the possible mechanism of agarwood broken wall pieces and traditional pieces for repairing gastric tissue damage were discussed.Methods:1.Determination of Agarwood Broken Pieces,Traditional Alcoholic Leachables and Agarwood Tetraol95%ethanol was used as a solvent,and its alcohol-soluble extractives were measured and compared by a hot dip method.An HPLC method was established to determine the index component agarwood tetraol,and the contents were compared.2.A Comparative Study on the Analgesic Effects of Agarwood Broken Pieces and Traditional Pieces on MiceThe hot plate method and writhing method were used to determine the pain threshold and the number of writhing times in mice.The degree of response of mice to pain was observed under the intervention of Agarwood broken pieces and traditional pieces.3.A Comparative Study of Agarwood Broken Pieces and Traditional Pieces on Gastrointestinal Motility in MiceThe gastric emptying method and small intestine advancing method were used to determine the gastric residual rate and small intestinal advancing rate in mice,and the effects of Agarwood broken pieces and traditional pieces on gastrointestinal movement were observed.4.A comparative study on the anti-gastric ulcer effect of Agarwood broken wall pieces and traditional pieces①An acetic acid-type chronic gastric ulcer model was established,and changes in body weight,organ coefficient,and gastric ulcer area were compared between the groups.②He staining,pathological changes of gastric tissue lesions in each group were observed under the microscope.③ELISA kit was used to detect the changes of EGF,TGF-α,IL-6,TNF-α in rat serum and EGF and TGF-α in gastric tissue.④The expression of EGF-R in gastric tissue was observed by immunohistochemistry.Results:1.Determination of Agarwood Broken Pieces,Traditional Alcoholic Leachables and Agarwood TetraolThe alcohol-soluble extract of Agarwood broken pieces is between 24%～30%,and agarwood tetraol is between 0.72%～0.74%.Agarwood traditional decoction alcohol extract is about 22%,agarwood tetraol is between 0.63%～0.64%.The non-scented white woody alcohol extract was only 6%～8%,and no agarwood tetraol was detected.The stability(24h)and repeatability test of Agarwood broken pieces and traditional pieces have RSD values of<2%(n=6),and the sample recovery rates are 100.4%and 102.1%,and the RSD values are<2%(n=6).2.Comparison of analgesic effects of Agarwood broken wall pieces and traditional pieces on mice①With time,there was no significant change in the blank group.The pain threshold of each administration group increased first and then decreased.The indomethacin group showed the greatest pain threshold at 1.5h after administration,and the rest of the administration groups reached the pain threshold at 2h after administration.The maximum,and then the pain threshold gradually decreases with time.The median of the basic pain threshold of each group were:12.43,17.04,13.79,15.11,15.52,16.49,16.02s.0.5h after administration,the pain threshold of Aquilaria 1/4 times broken wall pieces was the largest.After administration 1,the indomethacin group had the largest pain threshold.1.5h after the last administration,the pain threshold of the indomethacin group was the largest.2h after the last administration,the threshold of pain of Aquilaria lx broken wall pieces was the highest.2.5h after the last administration,the threshold of pain in the 1/2 times broken wall pieces of agarwood was the largest.3h after the last administration,the threshold of pain of 1/4 times the broken slices of agarwood was the largest.②The number of twists in the blank group was 34.9 ± 6.62 times.The indomethacin group,the traditional agarwood piece group,the agarwood 1x broken wall piece group,the agarwood 1/2 times broken wall pieces,the agarwood 1/4 times broken wall pieces,Agarwood 1/8 times b broken wall pieces,the twist times of each group were:14.4±5.93,20.3±5.85,19.1 ±4.82,20.2±4.96,17.7±3.5,26.9±6.12(s),which was significantly lower than the blank group(P<0.01).3.A Comparative Study of Agarwood Broken Pieces and Traditional Pieces on Gastrointestinal Motility in Mice①The gastric residual rate in the blank group was 71.79%.The gastric residue rate of domperidone group,agarwood traditional decoction group,agarwood 1 times broken wall decoction group,agarwood 1/2 times broken wall pieces,agarwood 1/4 times broken wall pieces,agarwood 1/8 times broken wall pieces respectively Out:22.44%,28.21%,34.29%,25.64%,36.54%,40.06%.Compared with the blank group,the gastric residual rate decreased significantly(P<0.01).②Compared with the blank group,the small intestine advancing rate of the domperidone group,agarwood 1 broken wall group,agarwood 1/2 times broken wall pieces,and agarwood 1/4 times broken wall pieces was significantly improved(P<0.01),and the small intestine advancing rate of traditional agarwood tablets was significantly improved.(P<0.05),the small bowel advancing rate of Agarwood 1/8 times broken wall pieces did not increase significantly(P>0.05).The intestinal propulsion rate of a quarter dose of agarwood broken pieces is similar to that of agarwood traditional pieces,and it is higher than that of agarwood traditional pieces.Its small intestine propulsion rates are 54.15±15.57%and 54.15 ± 15.57%.4.A comparative study on the anti-gastric ulcer effect of Agarwood broken wall pieces and traditional pieces①Observe the body weight changes of each group 1d before modeling,1d,3d,5d,7d,10d,and 14d.The weight of rats in each group increases with time,but the weight gain of the model group is greater than that of the administration group and sham operation group Slow weight gain.It is suggested that the administration group can improve the weight loss of rats caused by gastric ulcer to varying degrees.There was no significant difference in body weight between the administration groups(P>0.05).②After the administration,the spleen coefficient and kidney coefficient were measured.Compared with the blank group,the spleen coefficient of the model group increased and the kidney coefficient decreased,suggesting that the model may cause concurrent effects of spleen edema and kidney atrophy.Compared with the model group,each administration group can reverse this effect.The spleen coefficient and kidney coefficient of agarwood broken wall decoction pieces were lower than those of agarwood traditional group.③No ulcer occurred in the blank group and the sham operation group.The gastric ulcer in the model group was obvious,and severe cases showed perforation.After administration,each administration group could repair the gastric tissue damage caused by modeling.The area of gastric ulcer in the model group was 4.92mm2,the area of gastric ulcer in the omeprazole group,traditional agarwood group,agarwood 1 times broken wall pieces group,agarwood 1/2 times broken wall pieces was 0.71,2.56,0.84,2.78mm2,Compared with the model group,the gastric ulcer area was significantly and significantly reduced(P<0,01),and the area of gastric ulcer in the 1/4 times broken wall pieces of Agarwood was 2.44 mm2,respectively.Compared with the model group,the gastric ulcer area was significantly reduced(P<0.05).The area of gastric ulcer in rats of Aquilaria 1/8 times broken wall pieces was 3.79mm2,and the area of gastric ulcer was not significantly reduced compared with the model group(P>0.05).④Histopathological observation showed that there were no abnormalities in the blank group and the sham operation group.In the model group,focal necrosis of gastric mucosa glands and infiltration of inflammatory cells in the gastric mucosa were observed under microscope.Sexual cell infiltration;gastric submucosal edema,inflammatory cell infiltration;muscularis necrosis,inflammatory cell infiltration,fibrous tissue hyperplasia with bleeding.Fibrous tissue hyperplasia occurred in all groups.⑤The levels of IL-6 and TNF-α in the serum of rats after modeling were significantly increased(P<0.01),and the levels of EGF,TGF-α and PGE2 were significantly reduced(P<0.01).All dose groups of Agarwood can reduce the levels of IL-6 and TNF-α,and increase the levels of EGF,TGF-α and PGE2.The group of Aquilaria 1 times broken wall decoction can significantly reduce the levels of IL-6 and TNF-α(P<0.01),and significantly increase the levels of EGF,TGF-α and PGE2(P<0.01).The traditional agarwood group significantly increased PGE2 level(P<0.05),decreased IL-6 level(P<0.05),extremely significantly reduced TNF-α level(P<0.01),and significantly increased EGF and TGF-αlevels(P<0.01)The agarwood 1/2 times broken wall pieces can significantly reduce the levels of IL-6 and TNF-α(P<0.01),increase the levels of EGF and TGF-α(P<0.01),and significantly increase the levels of PGE2(P<0.05).The levels of IL-6 and TNF-α were significantly decreased in the agarwood 1/4 times broken wall pieces and agarwood 1/8-times broken wall pieces(P<0.01),while the levels of TGF-α and PGE2 were not significant(P>0.05).⑥After modeling,the content of EGF and TGF-α in rat gastric tissue decreased(P<0.05),and the expression of EGFR decreased(P<0.05).The levels of EGF and EGFR in gastric tissue of Aquilaria traditional group were not significantly increased(P>0.05),and the level of TGF-α was significantly increased(P<0.01);the level of EGF and TGF-α in gastric tissue of Aquilaria 1 times broken wall decoction group was significantly increased(P<0.01),the EGFR level was not significantly increased(P>0.05);the Agarwood 1/2-times broken wall pieces significantly increased the EGF level,very significantly increased the TGF-α level(P<0.01),and the EGFR level was not significantly increased(P>0.05);the levels of EGF and EGFR in the agarwood 1/4 times broken wall pieces of and agarwood 1/8 times broken wall pieces were not significantly increased(P>0.05),and TGF-α was significantly increased(P<0.01).Conclusions:①Agarwood wall-breaking decoction pieces and traditional decoction pieces have reached the pharmacopoeial standards in terms of alcohol-soluble extract content and agarwood tetraol content,and the alcohol-soluble extract content and agarwood tetraol content of agarwood wall-breaking pieces are higher than agarwood.Traditional pieces.②Agarwood broken wall tablets can effectively prolong the pain threshold of mice,reduce the number of twists in mice,promote gastrointestinal emptying,accelerate the intestine,and promote the healing of gastric ulcers.And at the same dose,the efficacy of agarwood broken pieces is better than that of traditional pieces,and even 1/2 times the dose of agarwood broken pieces can reach the effect of traditional agarwood pieces.③The mechanism by which Agarwood broken wall pieces can protect gastric injury may be:PGE2 level is up-regulated,IL-6,TNF-α expression is suppressed,EGF,TGF-α,EGFR expression is promoted,ulcer base contraction is accelerated,epithelial cell regeneration is promoted,granulation tissue formation is promoted,Generate blood vessels and increase blood flow to the mucosa,thereby promoting the healing of gastric ulcers.④ Agarwood Broken Pieces Supplementary Application Agarwood Traditional Pieces are worthy of clinical application... |
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