Medicine in Novel Technology and Devices 16 (2022) 100187

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Medicine in Novel Technology and Devices

journal homepage: www.journals.elsevier.com/medicine-in-novel-technology-and-devices/

A randomized clinical efficacy trial of Hehui capsule against hyperlipidemia

Ruiting Ma a, b, 1, Yuanyuan Ma c, 1, Junchan Qiao d, Lixia Chen a, **, Mingxing Hou c, *
a
Clinical Lab Department, Inner Mongolia Autonomous Region Mental Health Center, Hohhot 010010, China
b
Life Sciences Department. Nanjing Normal University, Nanjing 210026, China
c
Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
d
Inner Mongolia Medical University, Hohhot 010020, China

A R T I C L E I N F O A B S T R A C T

Keywords: Hehui capsule (Hhc) has been used as an assistant treatment for hyperlipidemia. According to the previous
Hyperlipidemia studies, miltiorrhiza and Chavica roxburghii may reduce the serum lipid level. This study aims at examining the
Hehui capsule (Hhc) efficiency of Hehui capsule with regards to treating hyperlipidemia in a randomized control, double-blind clinical
Auxiliary lowering blood lipid
trial. In the research, we assigned 104 eligible subjects to Hehui capsule group and placebo groups (52:52,
respectively). Subjects used self-control and inter-group controls to compare serum total cholesterol (TC), tri-
glyceride (TG), high-density lipoprotein cholesterol (HDL) and other changes before and after the test group and
the test group and the control group. During the 45 days intervention, 101 cases were actually included, among
which 51 cases for test group, and other 50 cases for placebo group. The total effective rate of blood lipid
reduction (90.20%) in the test group was significantly higher than that in the control group (26.00%) (P < 0.01).
Together, the result indicates that Hhc has a certain curative effect on dyslipidemia, with no obvious adverse
reactions, which can be developed into a new drug for hyperlipidemia.

1. Introduction blood circulation and relieving pain, removing blood stasis and
dysmenorrhea, clearing the heart and removing dryness [9–11]. After
Cardiovascular disease (CVD) is the leading cause of death among being extracted and refined by modern science and technology, the raw
adults in the United States [1–3]. Currently, hyperlipidemia is the main materials were processed to Hhc to help reduce blood lipid.
cause of CVD [2]. Hyperlipidemia belongs to lipid metabolism disorder, In this study, a randomized controlled, double-blind clinical trial was
including elevated levels of total cholesterol (TC), low-density lipopro- used to analyze and evaluate the HHc on regarding lowering serum lipid
tein (LDL), triglyceride (TG) and low levels of high-density lipoprotein level. That will provide theoretical support for clinical application of Hhc
(HDL) [3,4]. However, Hyperlipidemia might be caused by gene muta- on hyperlipidemia treatment.
tion (familial or primary hyperlipidemia), poor diet or other specific
factors (secondary hyperlipidemia), e.g., diabetes and obesity [5,6]. 2. Materials and methods
Therefore, early detection and treatment are necessary for reducing
cardiovascular events and premature death. Currently, statins are the 2.1. Subjects
main treatment for hyperlipidemia [7]. However, statins have much
limitation, including treatment resistance, intolerance due to adverse A double blinded, randomized controlled trial was conducted in 104
events, or lack of compliance with poor prognosis [8]. Miltiorrhiza, potential subjects who met the criteria (LDL >100 mg/dl, TC > 200 mg/
Chavica and sea-buckthorn are the main raw material of Hehui capsule dl, TG > 450 mg/dl) from July 2010 to December 2012 [11]. To select
(Hhc), which are homology of medicine and food. For example, Materia subjects, we interviewed them by internal medicinal physicians at the
Medica recorded that Salvia miltiorrhiza had the function of promoting Affiliated Hospital of Inner Mongolia Medical University in a preliminary

* Corresponding author.
** Corresponding author.
E-mail addresses: lixiachen2022@126.com (L. Chen), houmingxingfy@126.com (M. Hou).
1
These authors contributed equally to this work.

https://doi.org/10.1016/j.medntd.2022.100187
Received 31 August 2022; Received in revised form 22 October 2022; Accepted 26 October 2022
2590-0935/© 2022 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
R. Ma et al. Medicine in Novel Technology and Devices 16 (2022) 100187

screening. 104 subjects were randomly assigned into two groups (54 original living and eating habits remained unchanged. The observation
subjects as Hhc group, 54 subjects as placebo groups, receiving Hhc lasted for 45 days.
containing either placebo every day for 45 days. 3 subjects were with-
drawn before blood sample collection of the following reasons: diar- 2.4. Outcome measurements
rhoea, taking other blood lipid-lowering drugs (Fig. 1).
General situation: This includes mental health, sleep, diet, urine and
2.2. The sample feces, blood pressure, etc.
Dietary observation: before and after the start and end of the trial, the
Hhc was provided by a company in Inner Mongolia with batch subjects were informed about their dietary status before and during the
number 20160401 (registration mark: GuoshijianzhuG20150134). The trial. In order to eliminate the influence of dietary factors on the results of
contents are yellow-brown to tan granules and powder, 320mg/grain. the trial, the subjects were required to conform to their daily diet as much
The main functional components are salvianolic acid B and piperine. The as possible during the trial.
recommended dosage for human body is: 3 times per day, 3 pills per time, Safety observation: safety observation including blood, urine, stool
that is 2.88 g per person per day. The contents of placebo were yellowish- routine inspection (blood routine observation index of red blood cell
brown to tan granules and powder, and the main raw material was starch; count (RBC), white blood cell count (WBC), the content of hemoglobin
Its appearance, color, dose, dosage form and taste are basically consistent (Hb), liver and kidney function check (hepatorenal function outcome for
with hui capsule. the cereal third transaminase (ALT), aspertate aminotransferase (AST),
Patients/participants provided written informed consent to partici- creatinine (Cr), urea nitrogen (BUN), etc.). Chest X-ray, electrocardio-
pate in this study. The studies involving human participants were gram (ECG), and abdominal ultrasound examination operated before the
reviewed and approved by the Ethics Committee on Human Research of start of the test only once, other indicators to try before eating and food
the Affiliated Hospital of Inner Mongolia Medical University (Hohhot, after the end of the test again.
China) (approval number: ZS-2560). Efficacy observation: Serum total cholesterol (TC), triglyceride (TG)
Some subjects were dropped before blood sample collection of the and high-density lipoprotein cholesterol (HDL) were tested once at the
following reasons: (1)take other replacement therapy, (2) take the lipid beginning and end of the trial diet. Efficient criterion: Valid: TC reduces
regulating drugs, (3) take the drugs known to affect lipid concentrations, > by 10%; TG decreased > by 15%; HDL increased >0.104 mmol/L.
(4) take the drugs known to be associated with rhabdomyolysis, car-
diovascular disease, severe systemic and chronic disease, malignant 2.5. Statistical analysis
neoplasm, (5) pregnancy, (6) receive insulin or oral hypoglycemic agents
(7) have an endocrine disease related to lipid abnormalities. Meanwhile, We applied a Kruskal–Wallis test to measure significant differences in
another eight subjects discontinued intervention because of conventional the blood biochemical data respectively before intervention among the
medication preference during the study. two groups. Rank sum test was applied for data with homogeneous
variance but too large coefficient of variation (e.g., CV>50%). Efficiency
and total efficiency were tested by X2. All analyses were performed by
2.3. Intervention
using analytical software, GraphPad 8.0.

Persons with total serum cholesterol (TC)
5.2 mmol/L or serum

3. Results
triglyceride (TG)
1.65 mmol/L for 2 times within half a year, aged
18–65, male and female, can be selected as subjects to participate in
3.1. General situation
human trial food test according to voluntary principle. 104 patients with
simple dyslipidemia meeting the inclusion criteria were randomly
Among the test eaters, there were 3 cases that failed to insist on taking
divided into two groups according to the subjects' lipid level, double-
this product and left the test eaters, 1 case in the test group and 2 cases in
blind control group (52:52), and the test group (52 patients) were
the control group. 101 cases actually completed the test, including 51
given Hhc. The test group was given Hhc, while the control group was
cases in the test group and 50 cases in the control group. The comparison
given placebo, 3 pills each time, 3 times a day. During the test, the
of age, gender, blood pressure and blood lipid level between the two
groups before the food test is shown in Table 1. The comparison between
the two groups is conducted by t-test, and there is no significant differ-
ence in age, gender, blood pressure and blood lipid level between the two
groups before the food test (P > 0.05), suggesting comparability. During
the test, the subjects were mentally normal, their diet was consistent with
their daily diet; there were no abnormal manifestations of sleep, chest X-
ray, b-ultrasound of abdomen and electrocardiogram before the test
(Fig. S1).

3.2. Primary outcome measures

3.2.1. Total cholesterol

As shown in Table 1, total cholesterol in the test group decreased by
18.45% on average after the test (P < 0.01). The effective rate of total
cholesterol reduction was 76.47% in the test group and 6.00% in the
control group, with a highly significant difference (P < 0.01), which
suggested that Hhc can reduce total cholesterol.

3.2.2. Triglycerides
Tiglycerides in the test group decreased by 17.63% on average after
the test (P < 0.01). Compared with the control group, the difference was
Fig. 1. The flow chart of research process. significant (P < 0.05). The effective rate of triglyceride reduction was

2
R. Ma et al. Medicine in Novel Technology and Devices 16 (2022) 100187

Table 1
TC、TG、LDL、HDL decreased efficiency before and after taken (mmol/L ; x s).
Group Cases Before administration After administration Average rate of TC decline (%) Valid cases Invalid cases Effective rate

TC Trial group 51 5.69  0.88 3.59  0.78**ΔΔ 18.45  12.87ΔΔ 39 12 76.47%ΔΔ

control 50 5.67  0.55 5.65  0.60 0.43  4.69 3 47 6.00
TG Trial group 51 2.17  0.64 1.77  0.51**Δ 17.63  10.90ΔΔ 32 19 62.75ΔΔ
control 50 2.06  0.58 2.03  0.56 0.75  11.50 2 48 4.00
HDL Trial group 51 1.43  0.36 1.45  0.33 0.018  0.095 8 43 15.69
control 50 1.38  0.22 1.39  0.23 0.010  0.085 7 43 14.00
LDL Trial group 51 4.38  0.56 3.45  0.53 0.008  0.055 8 43 52.45ΔΔ
control 50 4.21  0.42 1.39  0.23 0.016  0.035 7 43 8.00

62.75% in the test group and 4.00% in the control group (P < 0.01), 3.3. Total effective rate
which suggested that Hhc can reduce triglyceride.
As shown in Table 2, Fig. 2, the total effective rate of lowering blood
3.2.3. High density lipoprotein cholesterol lipids in the test group after taking Hhc for 45 days was 90.20%, with a
There is no significant difference between the test group and the highly significant difference (P < 0.01) compared with the control group
control group before and after the high-density lipoprotein cholesterol (26.00%) (see Fig. 3).
test (P > 0.05). The effective rate of high-density lipoprotein cholesterol
increased was 15.69% in the test group and 14.00% in the control group
(P > 0.05).

Table 2
Total efficiency of lipids decreased.
Group Number Valid Invalid Effective rate P
sample sample

Trial group 51 46 5 90.20ΔΔ 0.000

Control 50 13 37 26.00
Δ Δ
Note：Chi-square test was used to compare the rates of the two groups. Fig. 3. Total efficiency of decreasing lipids.
compared with control group (P < 0.01).

Fig. 2. The results of serum lipid among the two groups before intervention and after intervention. A, TG. B, TC. C, HDL. D, LDL.

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R. Ma et al. Medicine in Novel Technology and Devices 16 (2022) 100187

Table 3
Blood safety indicators before and after Hehui capsule taken (mmol/L, x s).
items Experimental group （n ¼ 51） Control group（n ¼ 50）

Before administration After administration Before administration After administration

RBC (1012/L） 4.64  0.51 4.51  0.45 4.19  0.48 4.50  0.40
WBC (109/L） 5.20  1.20 6.08  1.34 5.22  1.27 5.86  1.08
HGB (g/L) 142.41  14.48 139.63  14.95 138.96  16.43 139.40  12.67
TP (g/L) 75.90  4.49 71.34  5.72 70.14  3.86 68.94  4.80
ALB (g/L) 48.26  2.41 46.87  4.48 46.75  3.06 43.73  5.29
AST (U/L) 25.51  8.02 23.53  7.04 25.49  8.10 25.44  8.12
ALT (U/L) 28.07  16.19 20.13  8.21 23.15  8.83 22.00  8.02
BUN (mmol/L) 5.07  1.21 5.20  1.13 5.38  1.21 5.47  1.10
Cr (μmol/L) 64.37  14.10 68.73  20.01 69.33  14.79 69.79  13.67
GLU (mmol/L) 4.82  0.98 5.03  0.58 4.98  0.57 4.79  0.59

3.4. Effect on human body safety index of lowering blood lipid in the test group (90.20%) was significantly
higher than that in the control group (26.00%), and the difference be-
No serious adverse effects were uncovered in any of the initial 104 tween the two was highly significant (P < 0.01). Before and after the test,
subjects randomly assigned. In the group, three subjects stopped due to blood, urine, stool routine, blood biochemistry and other indicators are
the minor adverse effects, including diarrhoea. within the normal range. Tip: Hhc has no obvious adverse effect on
Among the 101 potential subjects, no persons with liver enzyme subjects' health and has the function of assisting in lowering blood lipid.
elevation (SGOT/SGPT >34/36) were noted before the Hhc application.
They were equally distributed to the Hhc and the placebo group. 5. Conclusion
In the study, all the other collected data, including red blood cell
(RBC), white blood cell (RBC), hemoglobin (HGB), liver function test In this study, based on the methods of double-blind self and placebo
(total bilirubin, alkaline phosphatase, r-GT), electrolyte (sodium, potas- control design, we proved the curative effect of Hhc against Hyperlip-
sium, phosphorus, chloride, calcium), blood sugar, had minor variations idemia. At the same time, the other collected data, including red blood
between the two groups. The liver and renal function before, during and cell (RBC), white blood cell (RBC), hemoglobin (HGB), liver function e.g.,
after intervention was demonstrated in Table 3. tests were used to verify the Hhc was Non-toxic side effects. By doing this
research, we improved and developed the theoretical basis of Mongolian
4. Discussion medicine empirical prescription, laid the clinical foundation for its
research in the treatment of Hyperlipidemia.
Salvia miltiorrhiza, Piper longum, sea-buckthorn were the main medic-
inal materials of Hhc. Koubaa-Ghorbel reported [12] the protective effects Data availability statement
of Salvia officinalis essential oil compared to simvastatin against hyper-
lipidemia, liver, and kidney injuries in mice submitted to a high-fat diet. The raw data supporting the conclusions of this article will be made
A systematic review showed Salvia miltiorrhiza was the efficacy and safety available by the authors, without undue reservation, to any qualified
of herbal medicines used in the treatment of hyperlipidemia [13–16]. At researcher.
the same time, Sivanesan Raja Kumar proved methanolic Extract of Piper
sarmentosum Attenuates Obesity and Hyperlipidemia in Fructose-Induced Funding statement
Metabolic Syndrome Rats [17–21]. Many researchers also showed sea--
buckthorn has a curative effect on against hyperlipidemia [22–26]. The present study was supported by Inner Mongolia Medical Uni-
Double-blind self and placebo control design was used on 104 versity “Zhiyuan” talent plan “research” talents- -class one (ZY0110015).
voluntary subjects with simple dyslipidemia who met the inclusion
criteria, The subjects were randomly divided into two groups according Credit author statement
to their blood lipid levels, namely, the test group (52 cases) and the
control group (52 cases). The two groups were given Hhc and placebo, 3 Mingxing Hou, LIxia Chen did the work: Conceptualization; Data
pills each time, 3 times a day. During the observation, the original living curation; Formal analysis; Funding acquisition. Ruiting Ma: Investiga-
and eating habits were maintained. After 45 days, there were 3 patients tion; Methodology; Project administration; Resources; Software, Jun-
who failed to adhere to this product and separated from the test subjects, Chan Qiao: provided the clinical samples, Supervision and Validation,
1 in the test group and 2 in the control group. 101 cases actually Ruiting Ma: Visualization; Roles/Writing - original draft. Yuanyuan Ma:
completed the test, including 51 cases in the test group and 50 cases in Writing – review & editing.
the control group. The results showed that: (1) the comparison of serum
total cholesterol before and after the test group took Hhc for 45 days was Funding source
highly significant (P < 0.01), and the average decrease after the test
group took Hhc was 18.45%. Compared with the control group, the All sources of funding should also be acknowledged and you should
effective rate of serum total cholesterol was highly significant (P < 0.01). declare any involvement of study sponsors in the study design; collection,
(2) There was a highly significant difference between triglyceride test analysis and interpretation of data; the writing of the manuscript; the
and triglyceride test (P < 0.01). Compared with the control group, the decision to submit the manuscript for publication. If the study sponsors
difference was significant (P < 0.05). And the average decrease after the had no such involvement, this should be stated.
trial was 17.63%. Compared with the control group, the triglyceride
effective rate of the test group was highly significant (P < 0.01). (3)
There was no significant difference between the high-density lipoprotein Declaration of competing interest
cholesterol test and the control group (P > 0.05). The total effective rate
The authors have declared that no competing interest exists.

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R. Ma et al. Medicine in Novel Technology and Devices 16 (2022) 100187

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