Research Article

J Med Discov (2019); 4(2):jmd19010; DOI:10.24262/jmd.4.2.19010; 
Received May 8th, 2019, Revised June 10th, 2019, Accepted June 18th, 2019,  Published July 15th, 2019.

Effects of Kudiezi injection on diabetes patients complicated with cerebral infarction and bone mineral density

Zeyuan Li¹, Ruilian Ma^2*, Lidao Bao^2*

¹Department of Pharmacy, Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010059, P. R. China

²Department of Pharmacy, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010059, P. R. China

* Correspondence: Lidao Bao and Ruilian Ma. Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, 010059, P. R. ChinaTel: 86-4713451717. E-mail: lidao_bao@163.com

Objective: To observe the clinical effects of Kudiezi injection on diabetes patients complicated with cerebral infarction and their bone mineral density.

Methodology: One hundred diabetes patients complicated with cerebral infarction were randomly divided into a control group and a treatment group. The control group was intravenously injected with 250 ml of 0.9% NaCl injection containing 0.5 g meclofenoxate (qd). The treatment group was intravenously administered with 250 ml of 0.9% NaCl injection containing 40 ml of Kudiezi injection (qd). The two groups were treated for 21 d to observe the therapeutic effects and safety.

Results: There were no intra-group or inter-group difference between the clinical and biochemical indices of the two groups on the 21st day (P>0.05). The overall effective rate of the treatment group was significantly higher than that of the control group (P<0.05), and the neurological deficit score was significantly lower (P<0.05). The blood rheology indices and cerebral blood flow of the treatment group were better than those of the control group (P<0.05). Both treatments significantly elevated the bone mineral density (P<0.05), and the treatment group enjoyed significantly better outcomes (P<0.05). No adverse reactions occurred.

Conclusion: Kudiezi injection in combination with meclofenoxate could treat diabetes complicated with cerebral infarction safely and effectively.

Keywords: Kudiezi injection; diabetes mellitus; cerebral infarction; bone mineral density.

As one of the independent risk factors of cerebral infarction, diabetic mellitus severely endangers human life and health. Diabetes patients are prone to cerebral infarction simultaneously with increasing prevalence of diabetes and population ageing[1]. Such patients are commonly treated by thrombolysis, fibrinolysis and inhibition of platelet aggregation. However, these protocols are limited in clinical practice due to the harsh requirements of time window[2]. Recently, acute cerebral infarction has been successfully treated by promoting brain metabolism, increasing cerebral blood flow and mitigating neurological disorders, etc[3].

Kudiezi injection, which is refined with a Brassicaceae family herb Thlaspi arvense, mainly contains adenosine and flavonoids[4,5]. Kudiezi injection can scavenge oxygen free radical, prevent ischemia-reperfusion injury, dilates blood vessels, increase cardiac cerebral blood flow, elevate fibrinolytic activity, and improve microcirculation[6]. Besides, Kudiezi injection is capable of relieving clinical symptoms such as ischemic cardiovascular and cerebrovascular diseases, and angioneurotic headache[7]. Moreover, Kudiezi injection positively affects the microcirculation, peripheral neuropathy, diabetic nephropathy and bone mineral density of diabetes patients[8].

Therefore, this study aimed to evaluate the effects of Kudiezi injection on the diabetes patients complicated with cerebral infarction as well as their bone mineral density.

Table 1. Clinical and biochemical indices before and after treatment

General information

One hundred diabetes patients complicated with cerebral infarction who were diagnosed conforming to relevant standards within 3 days were selected. Cerebral infarction was confirmed by cranial CT. They were divided by random sampling into a treatment group and a control group. The treatment group included 27 males and 23 females aged 35-70 years old [mean: (52.8 ± 16.3)], and the control group included 26 males and 24 females aged 36-72 years old [mean: (54.2±15.7)]. The gender, age, risk factors of cerebrovascular diseases and disease severity of the two groups were similar (P>0.05).

Written consent has been obtained from all patients. Exclusion criteria: 1) Severe liver and kidney diseases, other bone metabolism disorders and administration of drugs affecting bone metabolism; 2) administration of calcium-containing drugs, lipid-lowering drugs and active vitamin D; 3) unwilling to take required drugs or incomplete clinical data.

Treatment methods

All patients were administered with diabetic diet while taking part in moderate exercises to control the fasting blood glucose level at 5.5-6.5 mmol/L and the postprandial glucose level at 6.5-9.5 mmol/L by injecting insulin and/or orally administering antidiabetic agents. The patients with high blood pressure level, high blood lipid level, intracranial hypertension and infections were first treated correspondingly. In addition, the control group was intravenously injected with 250 ml of 0.9% NaCl injection containing 0.5 g meclofenoxate (Nanjing Hicin Pharmaceutical Co., Ltd.) (qd). The treatment group was intravenously administered with 250 ml of 0.9% NaCl injection containing 40 ml of Kudiezi injection (ShenYang Shuangding Pharmacy Co., Ltd.) (qd). The two groups were treated for 21 d to observe the therapeutic effects and safety.

Main clinical indices

The changes of blood rheology, cerebral blood flow, blood test items, electrolyte levels and liver, kidney functions before and after treatment were compared. The plasma levels of C-reactive protein (CRP) and interleukin-6 (IL-6) were detected. Moreover, adverse reactions were observed and recorded.

Bone mineral density was measured by OSTEOCORE dual-energy X-ray absorptiometry (MEDILINK, France) at the the neck, Torch and Ward’s triangle of femur of the non-dominant side, as well as the 1st-4th lumbar vertebrae. The machine was corrected daily before measurements (accuracy: 1%; measurement error: <1%).

Table 2. Therapeutic effects

Evaluation criteria for therapeutic effects

The therapeutic effects were graded according to the following criteria. Basically cured: Neurological deficit score decreases by 91%-100% (degree of disability: 0); significantly improved: neurological deficit score decreases by 46%-90% (degree of disability: 1-3); improved: neurological deficit score decreases by 18%-45%; unchanged: neurological deficit score decreases by approximately 17%; aggravated: neurological deficit score increases by over 18%. Overall effective rate = (Case number of basically cured patients + case number of significantly improved patients + case number of improved patients)/(total case number) × 100%[9].

Statistical analysis

All data were analyzed by SPSS 15.0 and expressed as x(-)±s (means ± standard deviation). The two groups were compared by t test. P<0.05 was considered statistically significant.

Clinical and biochemical indices before and after treatment

The BMI, PT, APTT, TT and FIB of the two groups (both inter-group and intra-group) were similar after 21 days of treatment (P>0.05) (Table 1).

Table 3. Blood rheology indices

Compared with the results before treatment, *P<0.05; compared with the control group, #P<0.05.

Therapeutic effects

The overall effective rates of the treatment group and the control group were 86.00% and 64.00% respectively, which were significantly different (P<0.05) (Table 2).

Blood rheology indices

Whole blood viscosity, hematocrit and platelet viscosity were significantly different before and after treatment (P<0.05), and the fibrinogen level of the treatment group after treatment was also significantly different from that before treatment (P<0.05). After treatment, the whole blood viscosity, hematocrit, platelet viscosity and fibrinogen level of the treatment group were significantly different from those of the control group (P<0.05) (Table 3).

Cerebral blood flow

Both groups had significantly different cerebral blood flows after treatment compared with those before treatment (P<0.05). Moreover, most associated indices of the two groups were also significantly different (P<0.05) (Table 4).

Table 4. Cerebral blood flow

Compared with the results before treatment, *P<0.05; compared with the control group, #P<0.05.

Serum CRP and IL-6 levels

CRP levels of both groups were reduced by 18.5% and 45.9% respectively after treatment, and IL-6 levels were decreased by 13.1% and 9.3% respectively (P<0.05). After treatment, CRP levels of the two groups were also significantly different (P<0.05) (Table 5).

Bone mineral density

Bone mineral densities of both groups were significantly raised after 21 days of treatment (P<0.05), and the two groups also had significantly different outcomes after treatment (P<0.05) (Table 6).

Table 5. Serum CRP and IL-6 levels

Compared with the results before treatment, *P<0.05; compared with the control group, #P<0.05.

Table 6: Bone mineral density

Compared with the results before treatment, *P<0.05; compared with the control group, #P<0.05.

Diabetes complicated with cerebral infarction occurs owing to complicated reasons, for which hyperglycemia may be a crucial risk factor. Besides, abnormal blood flow pattern and flow rate may also contribute to the devastating disease, and cerebral microcirculation can be reflected by dynamic blood rheological changes[10,11] that are closely associated with the aggregation and deformability of red blood cells and platelets, as well as plasma composition. After cerebral infarction, cerebral vascular occlusion decreases blood flow by inducing regional hypoperfusion or drying up and cerebral edema. Therefore, brain cell functions are severely damaged due to long-term ischemia that weakens the oxygen storage capacity, thus jeopardizing partial functions of normal cells and metabolism[12,13].

As an age-related disease, osteoporosis is mainly manifested as reduced mechanical strength of bone and loss of coupling between bone formation and resorption[14]. It has previously been reported that elderly men with type 2 diabetes suffered from significant decrease in bone mineral density, with the bone metabolism characteristics of increased bone resorption and decreased bone formation[15]. In addition, the patients with diabetic nephropathy were prone to bone fracture. As secondary osteoporosis, diabetic osteoporosis may be another chronic complication of diabetic mellitus, which has not been verified hitherto though[16]. However, bone fracture is bound to affect the quality of life of diabetes patients[17,18]. Hence, it is of great significance to treat diabetic osteoporosis.

Kudiezi injection, which is extracted, separated and refined from the whole herb of a Brassicaceae family plant Thlaspi arvense, mainly contains adenosine and flavonoids[19]. The injection can resist platelet aggregation, inhibit thrombosis, enhance fibrinolytic activity, promote thrombolysis, dilate blood vessels, reduce vascular resistance, increase cardiac cerebral blood flow, stabilize cell membrane and protect nerve functions[20].

In this study, the blood rheology indices and cerebral blood flows of both groups were significantly improved after treatment (P<0.05). In the meantime, the treatment group had significantly better outcomes than the control group did (P<0.01 or P<0.05). The overall effective rates of the treatment group and the control group were 86.00% and 64.00% respectively, which were significantly different (P<0.05).

In summary, Kudiezi injection could resist platelet aggregation, facilitate thrombolysis, improve cerebral circulation, protect nerve functions, effectively decrease the levels of serum CRP and IL-6, and suppress the release of inflammatory mediator. This injection gave rise to satisfactory outcomes for diabetes complicated with cerebral infarction while being fairly secure. Furthermore, it elevated the bone mineral density of type 2 diabetes patients without inducing coagulopathy, and it could be used to treat type 2 diabetes complicated with osteoporosis in combination with calcium reagents.

The authors declare no competing financial interest.

None

1. Inagaki K, Nagao M, Oikawa S. Internal medicine and neurological diseases: progress in diagnosis and treatment. Topics: II neurological diseases related to diabetes mellitus; 2. Cerebral infarction, coma, hypoglycemia. Nihon Naika Gakkai Zasshi. 2012;101(8):2180-7.
2. Bouchi R, Babazono T, Takagi M, Yoshida N, Nyumura I, Toya K, et al. Non-linear association between ankle-brachial pressure index and prevalence of silent cerebral infarction in Japanese patients with type 2 diabetes. Atherosclerosis. 2012;222(2):490-4.
3. Zhang B, Gao C, Hou Q, Yin J, Xie L, Pu S, et al. The potent different risk factors for cerebral infarction in young patients with and without type 2 diabetes: subanalysis of the Young Cerebral Infarction Study (YCIS). Atherosclerosis. 2012;221(1):215-20.
4. Wang JL, Lv D, Liang XY, Zhao M, Zhang SJ. Study on chemical constituents of the Ixeris chinensis. Zhong Yao Cai. 2011;34(11):1706-8.
5. Zhang N, Lv AL, Zheng Z, Zeng YM, Li YN, Pei YH. Two new compounds from Ixeris sonchifolia. J Asian Nat Prod Res. 2008;10(3):211-5.
6. Song SJ, Zhou LY, Li LZ, Gao PY, Jia WW, Peng Y. Two new sesquiterpene lactones from Ixeris sonchifolia. Nat Prod Commun. 2011;6(8):1055-7.
7. Trinh HT, Bae EA, Hyun YJ, Jang YA, Yun HK, Hong SS, et al. Anti-allergic effects of fermented Ixeris sonchifolia and its constituent in mice. J Microbiol Biotechnol. 2010;20(1):217-23.
8. Ceylan-Isik AF, Fliethman RM, Wold LE, Ren J. Herbal and traditional Chinese medicine for the treatment of cardiovascular complications in diabetes mellitus. Curr Diabetes Rev. 2008;4(4):320-8.
9. Nina VJ, Rocha MI, Rodrigues RF, Oliveira VC, Teixeira JL, Figueredo ED, et al. Assesment of CABDEAL score as predictor of neurological dysfunction after on-pump coronary artery bypass grafting surgery. Rev Bras Cir Cardiovasc. 2012;27(3):429-35.
10. Ichikawa H, Shimizu Y, Kuriki A, Murakami H, Mukai M, Kawamura M. The brainstem is at high risk for recurrent noncardioembolic cerebral infarction in association with diabetes mellitus: a hospital-based study. Eur Neurol. 2012;67(1):26-32.
11. Katakami N, Kaneto H, Osonoi T, Kawai K, Ishibashi F, Imamura K, et al. Transforming growth factor beta1 T868C gene polymorphism is associated with cerebral infarction in Japanese patients with type 2 diabetes. Diabetes Res Clin Pract. 2011;94(3):57-60.
12. Li G, Xu X, Wang D, Wang J, Wang Y, Yu J. Microglial activation during acute cerebral infarction in the presence of diabetes mellitus. Neurol Sci. 2011;32(6):1075-9.
13. Petzold S, Kapellen T, Siekmeyer M, Hirsch W, Bartelt H, Siekmeyer W, et al. Acute cerebral infarction and extra pontine myelinolysis in children with new onset type 1 diabetes mellitus. Pediatr Diabetes. 2011;12(5): 513-7.
14. Xia J, Zhong Y, Huang G, Chen Y, Shi H, Zhang Z. The relationship between insulin resistance and osteoporosis in elderly male type 2 diabetes mellitus and diabetic nephropathy. Ann Endocrinol (Paris). 2012;73(6):546-51.
15. Takeuchi Y. Diabetes mellitus and osteoporosis. Therapeutic strategy for osteoporosis in patients with diabetes mellitus. Clin Calcium. 2012;22(9):1410-5.
16. Abdulameer SA, Sulaiman SA, Hassali MA, Subramaniam K, Sahib MN. Osteoporosis and type 2 diabetes mellitus: what do we know, and what we can do? Patient Prefer Adherence. 2012;6:435-48.
17. Bandeira E, Neves AP, Costa C, Bandeira F. Association between vascular calcification and osteoporosis in men with type 2 diabetes. J Clin Densitom. 2012;15(1):55-60.
18. Yamagishi S. Role of advanced glycation end products (AGEs) in osteoporosis in diabetes. Curr Drug Targets. 2011;12(14):2096-102.
19. Shi P, Zhang Y, Qu H, Fan X. Systematic characterisation of secondary metabolites from Ixeris sonchifolia by the combined use of HPLC-TOFMS and HPLC-ITMS. Phytochem Anal. 2011;22(1):66-73.
20. Cha MR, Choi YH, Choi CW, Yoo DS, Kim YS, Choi SU, et al. New guaiane sesquiterpene lactones from Ixeris dentata. Planta Med. 2011;77(4):380-2.

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