512

Journal of Health Science, 57(6) 512–520 (2011)— Regular Article —Korean Red Ginseng Extract Suppresses the Progression of
Alcoholic Fatty Liver in a Rat Model
Yoo-Sin Park and Ju-Seop Kang∗
Institute of Medical Science and Department of Pharmacology, College of Medicine; Division of Molecular Therapeutics Development,
Hanyang Biomedical Research Institute, Hanyang University, Haengdang-dong 17, Seoul, 133–791, Republic of Korea(Received June 7, 2011; Accepted September 18, 2011)

Alcoholic fatty liver (AFL) is the most common liver disease among Korean men, and Korean red ginseng has
been used as a folk medicine to diverse diseases in Korea. Therefore, we examined if Korean red ginseng extract(KRG) could be a suppressive agent on AFL in a rat model or not. Experimental rats were fed the Lieber DeCarli
diet with 36% of energy intake from ethanol, and divided into three groups which daily co-administered KRG 0,
700 and 1400 mg/kg for six weeks, respectively. Naive rats were fed iso-caloric control diet without ethanol and
KRG. We investigated histopathological hepatic characteristics, hepatic and plasma lipid concentrations, hepatichydroxyproline contents, heart/liver radioactivity ratio of 201 Thallium and liver/body weight of the rats at the end
point. Ethanol intake brought about steatotic, inflammatory, necrotic and fibrotic changes of livers significantly,
and it also lead the rats to increase hepatic triglyceride and hydroxyproline contents, plasma total cholesterol andlow density lipoprotein cholesterol levels, and liver/body weight. However, co-administration of KRG 1400 mg/kg
suppressed fat accumulation and fibrotic initiation in AFL rat model significantly. It was also inclined to attenuate
inflammatory cell infiltration, hydroxyproline accumulation, and increasing liver/body weight, even though plasma
lipid levels and heart/liver ratios were not successfully improved by six-week-long intakes of KRG. In conclusions,co-administration of KRG 1400 mg/kg could significantly suppress steatosis in AFL rat model, and it might needlonger ingestion of KRG than six weeks to improve plasma lipid imbalance.
Key words —— Korean red ginseng, alcoholic fatty liver, fibrosis

INTRODUCTION
In the East Asian countries including China,
Japan and South Korea, various folk remedies havebeen prescribed for the treatment of liver diseases. Researches are ongoing to define the preventive and curative properties of these natural materials such as Hoveniadulcis,1) Plantagoasiatica L.
seeds,2) and the fruits of Chrysanthemum indicum
Linné,3) Meliatoosendan fruit,4) and Schisandrachinensis Baill.5) Above all, Korean ginseng, the rootof Panax ginseng, has been prescribed as the mostprecious folk medicine in many oriental nations.
Therapeutic effects of Korean ginseng have been∗

To whom correspondence should be addressed: Institute ofMedical Science and Department of Pharmacology, Collegeof Medicine; Division of Molecular Therapeutics Development, Hanyang Biomedical Research Institute, Hanyang University, Haengdang-dong 17, Seoul, 133–791, Republic of Korea. Tel.: +82-2-2220-0652; Fax: +82-2-2292-6686; E-mail:jskang@hanyang.ac.kr

shown in a lot of studies on hyperlipidemia,6) tumors and cancers,7) oxidative stress,8) arthrosclerosis,9) hypertension,10) diabetes,11) and liver toxicity.12) The steamed and dried form of Korean ginseng, known as Korean red ginseng, is less-toxic,preserved longer, and has different bioactivities
when compared to fresh Korean ginseng.13, 14) Total
saponin contents including panaxadiol and panaxatriol are also increased in Korean red ginseng,13–15)
which have demonstrated protective effects on hepatotoxicity induced by carbon tetrachloride (CCl4 ),
acetaminophen, and high fat diets in animal studies.12, 16, 17) Due to these benefits on hepatotoxicity
of Korean red ginseng, it was considered to apply
to alcohol-induced hepatotoxicity such as alcoholic
fatty liver (AFL), the most prevalent disease among
over 55% of Korean men aged from forty to sixty
years old.18) AFL is the initial stage of liver cirrhosis related to heavy alcohol consumption,19) andthe subsequent onset of alcohol-induced liver diseases is the fourth leading cause of death followingC 2011 The Pharmaceutical Society of Japan

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No. 6

malignant carcinomas, cerebro-/cardiovascular diseases and respiratory diseases. It is also a cause ofsignificant morbidity before death, and a major expense to the healthcare system in Republic of Korea.20) Therefore, we examined if Korean red ginseng extract (KRG) has a suppressive potency on
progression of AFL in an animal model or not, prior
to clinical application.

MATERIALS AND METHODS
Animals and the Experimental Design —— Extract form of KRG was obtained from the Korea Ginseng Corporation (“Cheong Kwan Jang”, a
6-year-old Korean red ginseng root extract, with
crude saponin contents > 70 mg/g, assayed by government laboratory in Daejeon city, Republic ofKorea). Forty male Sprague-Dawley rats weighing
180–190 g were purchased from Central Laboratory
Animal Incorporation (Seoul, Republic of Korea),
divided into four groups and housed in plastic cages
at 23–25◦ C with a 12 hr light/dark cycle. The experimental protocol was approved by the Animal Careand Use Committee of Hanyang University (Seoul,
Republic of Korea). Experimental rats were fed aliquid diet containing 95% ethanol which provided
36% of the total energy intake for six weeks, while
naive rats were supplied an iso-caloric control dietaccording to the protocol of Lieber and DeCarli.21)
Dietary energy intake of naive rats were limited tothe average intake of the experimental rats. KRG
extract was orally administered to the experimental rats at the concentration of 0 (Ethanol + KRG
0 mg/kg group, n = 10), 700 (Ethanol + KRG
700 mg/kg group, n = 10) or 1400 mg/kg bodyweight (Ethanol + KRG 1400 mg/kg group, n = 10),once a day, five times per week, for six weeks.
Naive rats (naive group, n = 10) were given isovolumetric distilled water in the same manner, andbody weight (g) was also measured every week.
At the end of the experimental period, all the rats
were anesthetized with ether following a 12 hr fast.
Plasma was derived by centrifugation (3000 rpm,
15 min, 4◦ C) of blood samples obtained by heart
puncture. Livers were removed from the bodyand rinsed with normal saline solution. Then thesliced large lobes were fixed in 10% neutral bufferedformalin solution, while the remaining liver tissues were stored at −70◦ C for further examinations.
Liver/body weight (%) was calculated by “(liver(g)/body (g)) × 100.”

Histopathological Examination of Livers ——Fixed liver tissues were paraffin-embedded andsliced as thick as 4 µm. The sliced specimens wereHematoxyline & Eosin (H&E) stained and observed
by light microscopy (× 200) for the evaluationof steatosis, inflammation and necrosis. Hepatic
steatosis was evaluated by Tsutsumi and Takase’s
method22) which is described as the percentageof hepatocytes containing fat, such as, no fatty
degradation (grade 0), one third of hepatic lobules(grade 1), two thirds of the hepatic lobules (grade 2)
and the whole of the hepatic lobules (grade 3). Hepatic inflammation and necrosis were evaluated by
the presence and the distribution of the neutrophil
and necrotic cell infiltration23) which is described asabsent (grade 0, normal), scattered (grade 1, mild),
focal (grade 2, moderate) and diffuse (grade 3, severe). The sliced specimens were also Masson’s
Trichrome (MT) stained and observed by light microscopy (× 200) for the evaluation of fibrosis. Hepatic fibrosis was evaluated by Knodell’s scoring system24) which is described as ‘no fibrosis (grade 0),’‘fibrous pericentral expansion (grade 1),’ ‘bridging
fibrosis (grade 2),’ ‘fibrosis septa and structural disturbance of hepatic lobule (grade 3)’ and ‘cirrhosis (grade 4).’ The pathological alterations of both
H&E and MT stained specimens were evaluated andconfirmed by a certified independent pathologist.
Liver Function Tests and Lipid Concentrationsof Livers and Plasma —— Thawed liver tissues
were homogenized in chloroform-methanol solution (2 : 1, v/v) in ice-bath, and then centrifugedat 3000 rpm, 20 min, 4◦ C. The lower chloroform
fraction of the homogenized tissue was separated
and evaporated by nitrogen gas, then mixed vigorously with chloroform again and evaporated bynitrogen gas for purification.25) The purified lipids
were dissolved by chloroform-Triton X100 solution(19 : 1, v/v) and then analyzed by enzymatic spectrophotometry using commercial kits for triglyceride (Cleantech TG-S, Asan Pharm., Ltd., Hwasung city, Korea) and total cholesterol (T-CHO,
Asan Pharm., Ltd.) at 550 and 500 nm, respectively.26) Plasma total cholesterol and triglyceride
levels were determined using Olympus Analyzer(AU400, Olympus Corporation, Tokyo, Japan), andplasma high density lipoprotein (HDL) cholesterol
was determined by an enzymatic assay (HBi Co.,
Ltd., Anyang city, Korea). Low density lipoprotein(LDL) cholesterol was calculated from the equationof “LDL cholesterol = (Total cholesterol − HDLcholesterol − triglyceride)/5; unit = mg/dl).” Con-

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Table 1. Histopathological Evaluation of Steatosis, Inflammation, Necrosis, Fibrosis and Total Liver Scores in the
H&E and MT Stained Liver Tissues of the AFL Rat Model
Naive
Steatosis (%)
Steatosis
Inflammation
Necrosis
Fibrosis
Total scores21.24 ± 2.84a∗
1.20 ± 0.13a
0.90 ± 0.10a
1.10 ± 0.23a
0.40 ± 0.16a
3.30 ± 0.26a

KRG 0 mg/kg
48.35 ± 2.66b
2.00 ± 0.00b1.60 ± 0.16b2.40 ± 0.16b
1.00 ± 0.00b6.60 ± 0.40b

Ethanol +KRG 700 mg/kg
37.22 ± 3.16c
1.67 ± 0.17bc
1.20 ± 0.13ab
2.40 ± 0.16b
1.00 ± 0.00b6.10 ± 0.35cb

p-value
KRG 1400 mg/kg
35.36 ± 4.38c
1.38 ± 0.18ac
1.40 ± 0.16b
2.20 ± 0.20b
0.56 ± 0.18a
5.20 ± 0.47c

0.000
0.002
0.010
0.000
0.001
0.000

Mean ± S.E. Steatosis (0–3), inflammation (0–3), necrosis (0–3), fibrosis (0–4) and total liver scores (0–13). ∗ Each groupwhich has different superscript letters is significantly different each other in each row by ANOVA following Duncan post-hoc test at
p < 0.05.

centrations of alanine aminotransferase (ALT) andaspartate aminotransferase (AST) in plasma werealso determined to evaluate liver function using respective kits from Asan Pharm., Ltd.
Hydroxyproline Contents in Livers —— For theevaluation of liver fibrosis and collagen accumulation, hydroxyproline was determined in the liver tissues according to the modified method of Reddy
and Enwemeka.27) Thawed liver tissues were homogenized in 6 N hydrochloric acid solution andhydrolyzed in the autoclave at 121◦ C, 20 min. Aftercooling them to room temperature, the upper fractions of the liver hydrolysates, in triplicate, wereadded to separate vials, and allowed to evaporate todryness under nitrogen gas. The residues were dissolved in 50% isopropanol, with added 6.7% Chloramin T and Ehrlich’s solutions, then incubated at
60◦ C, for 20–90 min. After rapid cooling them incold water, hydroxyproline was assayed using spectrophotometer at 558 nm.
201 Thallium (Tl) per Rectum Scintigraphy ——To evaluate the portal pressure as a prognostic indicator of portal systemic shunt, 201 Tl per rectal
scintigraphy was performed in the rats according
to the procedure described by Tonami28) and Urbain.29) At the end of the experiment, rats were
fasted for 12 hr and then administered sodium phosphate enema through the rectum for 40–60 min under ether-anesthesia. After emptying the colon of
the rats, heart/liver radioactivity ratio of 201 Tl (H/L
ratio) was detected using Nuclear Gamma Camera
Siemens orbiter 7500 (Siemens medical solutions
U.S.A. Inc., Malvern, PA, U.S.A.) equipped withlow energy all purpose single head collimator at thesite of liver and heart regions after 18–20 minutesof intrarectal administration of 0.5 mCi 201 Tl. An
increased H/L ratio implies portal pressure change

caused by liver fibrosis.
Statistical Analysis —— All the measurements
were presented as mean ± S.E., and statistical significance among the groups was analyzed by analysis of variance (ANOVA) following Duncan posthoc test at p < 0.05 using SPSS version 17.0 program. Only weight data were analyzed by repeatedmeasured ANOVA through the study period at p <0.05.

RESULTS
Effects of KRG on Histopathological Characteristics in Livers
Histopathological analysis by H&E and MT
staining showed significant development of microor macro-vesicular steatosis, as well as necrosis accompanied by inflammatory cell infiltration in theethanol administered rats over the six weeks period (Fig. 1). Among the ethanol administered rats,
co-administration of KRG attenuated the deposition of fat effectively, and diminished inflammatory cells infiltration and necrosis in livers mildly,
while the worst evidence of liver injury was exhibited accompanying the greatest degree of fat
accumulation in 1/3–2/3 of the hepatic lobules,
scattered or focal neutrophils and necrotic cells
in liver tissues without co-administration of KRG(Fig. 1, H&E). The percentage of hepatosteatosis was evaluated as 21.24% for naive rats, andit was increased in the order of Ethanol + KRG
1400 mg/kg (35.36%), Ethanol + KRG 700 mg/kg(37.22%) and Ethanol + KRG 0 mg/kg (43.35%)
groups (p = 0.000, Table 1). Fibrous pericentral
expansion was also noticed in the Ethanol + KRG
0 mg/kg or Ethanol + KRG 700 mg/kg groups (p =

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Fig. 1. Histopathological Findings of H&E Stained or MT Stained Livers in the AFL Rat Model (× 200)
Black ovals indicate macrovesicular steatosis and black circles indicate microvesicular steatosis. Black arrows indicate inflammatory cell infiltration
with necrosis and white arrows indicate fibrotic changes.

0.001, Fig. 1, MT and Table 1). Overall antihepatosteatotic effect was stronger when KRG
1400 mg/kg was administered to the ethanolinduced rats, as the total liver score (p = 0.000)
which includes steatosis (p = 0.002), inflammation, necrosis and fibrosis (p = 0.001) exhibited(Table 1).
Effects of KRG on Hydroxyproline Contents in
Livers and H/L ratios by 201 Tl per Rectal Scintigraphy Test
Hepatic hydroxyproline contents are index ofcollagen accumulation which is a key componentof the fibrotic tissues observed in the alcoholic

liver diseases. The hepatic hydroxyproline contents
were significantly elevated after ethanol consumption, however co-administration of KRG 700 or
1400 mg/kg depressed mildly the deposit of hydroxyproline in livers (Table 2, p = 0.021). H/L ratios by
201 Tl per rectal scintigraphy were not significantly
changed by the administration of ethanol or KRG
for six weeks, even though Ethanol + KRG 0 mg/dl
and Ethanol + KRG 700 mg/dl groups had relatively
higher H/L ratios than naive and Ethanol + KRG
1400 mg/kg groups’ (Table 2).
Effects of KRG on Hepatic and Plasma Lipid
Concentrations, and Liver Function Markers

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Table 2. Hydroxyproline Contents (µg/g) in Livers and H/L Ratios by 201 Tl per Rectal Scintigraphy in the AFL Rat Model
Naive
Hydroxyproline
H/L ratio

279.50 ± 17.78a∗
0.187 ± 0.022

KRG 0 mg/kg
345.42 ± 10.84b
0.227 ± 0.024

Ethanol +KRG 700 mg/kg
308.88 ± 16.72ab
0.229 ± 0.020

p-value
KRG 1400 mg/kg
315.00 ± 8.50ab
0.199 ± 0.013

0.021
0.380

Mean ± S.E. ∗ Each group which has different superscript letters is significantly different each other in each row by ANOVA following
Duncan post-hoc test at p < 0.05.

Fig. 2. Comparisons of Hepatic Lipids, Plasma Lipids and Liver Function Markers in Plasma
Hepatic lipid contents (A), plasma lipid concentrations (B) and liver function markers (C) in the AFL rat model (mean ± S.E.). Each group which
has different alphabetical letters such as a, b, and c is significantly different each other by ANOVA following Duncan post-hoc test at p < 0.05.

The contents of triglyceride in livers (Fig. 2A)
were significantly increased in ethanol administeredrats, however co-administration of KRG 700 or
1400 mg/kg suppressed the hepatic accumulation of
triglyceride (p = 0.003). Specially, AFL was remarkably attenuated to the level of naive rats byco-administration of higher concentration of KRG(1400 mg/kg). Hepatic contents of total cholesterol(Fig. 2A) had a similar trend of triglyceride contents, even though it was not significantly. The
plasma total cholesterol and LDL cholesterol levels(Fig. 2B) were significantly increased in ethanol administered rats, however, co-administration of KRG
700 mg/kg suppressed the elevation of total cholesterol and LDL cholesterol levels in plasma mildly(p = 0.015 and 0.011, respectively). Plasma triglyceride and HDL cholesterol concentrations (Fig. 2B)
were not significantly influenced by ethanol or

KRG administration during the six-week experiment. Representative markers of liver function were
presented in Fig. 2C, and concentration of plasma
ALT was significantly increased in ethanol administered rats (p = 0.002). However, co-administrationof KRG prevented the elevation of ALT level inplasma, and the preventive effect was more significant when co-administered KRG 1400 mg/kg (p =0.002). Plasma AST level showed a same trendof ALT level, even though it was not significant
enough.
Effects of KRG on Liver/Body Weight Percentages
The body weights of the rats (Fig. 3A) were significantly increased after two weeks of the experiment when the time went by (p < 0.05 each). The
body weight each week of the naive rats (Fig. 3A)

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Fig. 3. Comparisons of Body Weight and Liver to Body Weight Percentages
Variations of body weight for six weeks (A) and liver to body weight percentages (B) in the AFL rat model (mean ± S.E.). A cross (†) indicatesthat mean body weight of the week is different from the weight of initial week at p < 0.05, and an asterisk (∗) indicates that mean body weight of naive
group is different from the ethanol administered groups’ each week at p < 0.05. Different letters mean the statistical differences of liver/body weight(%) among the groups by ANOVA following Duncan post-hoc test at p < 0.05. Each group which has different alphabetical letters such as a and b issignificantly different each other in its liver/body weight (%) by ANOVA following Duncan post-hoc test at p < 0.05.

was significantly heavier than the ethanol administered rats at the second, third, fifth and sixth weeks(p < 0.05 each). However, body weights were notdifferent among the ethanol administered rats. On
the contrary, the liver to body weight percentagesof the ethanol administered rats (Fig. 3B) were significantly higher than the naive rats, and the coadministration of KRG 1400 mg/kg could mildly attenuate the excessive liver mass (p < 0.05).

DISCUSSION
AFL, the initial stage of alcoholic liver diseases, is marked by fatty metamorphosis of hepatocytes which accumulate in the liver and which
are highly sensitive to further alcoholic insult leading to the development of more severe manifestations of alcohol-induced liver diseases such as
hepatitis, fibrosis and finally, cirrhosis.30, 31) In thecurrent study, interventional administration of theherbal medicine, KRG, had a magnificent antihepatosteatotic effect in AFL rat model when it wasorally administered for six weeks, and the protective
effect was proved by evaluation of histopathological characteristics (Fig. 1, H&E and Table 1), hepatic lipid contents (Fig. 2A) and liver/body weight(Fig. 3B). The anti-hepatosteatotic effect was sodose-dependent that KRG 1400 mg/kg was more
beneficial than KRG 700 mg/kg. In addition to theanti-hepatosteatotic effect, anti-inflammatory effectof KRG on AFL was also noticed (Fig. 1A and
Table 1). It was explained by dose-dependent de-creases of plasma ALT (p < 0.05) and AST levels which represented hepatocyte and mitochondrial injuries in livers, respectively (Fig. 2C), eventhough hepatic mitochondrial function was not distinctly altered during the six-week study. Fibroticchanges associated with more advanced stages ofalcoholic liver diseases were also significantly retarded by KRG co-administration (Fig. 1, MT and
Table 1), and it was supported by reduction of hepatic hydroxyproline contents, which represents hepatic collagen formation, in KRG co-administeredrats (Table 2). Even though the severity of fibrosis was not serious enough to elevate the hepatic
portal pressure (H/L ratio) during the six-week ofalcohol intake, it was meaningful that initiation offibrotic changes from AFL could be suppressed byadministration of KRG (Table 2). H/L ratios at
20 min after administration of 201 Tl were reported
that > 0.16 from ‘normal livers without alcoholic
damages,’ > 0.25 from ‘chronic hepatitis,’ > 0.40
from ‘alcoholic fatty liver without cirrhosis’ and> 0.92 from ‘cirrhosis with diverse hepatocellular
damages and significant differences.’28, 32)
Interestingly, plasma triglyceride and HDLcholesterol levels were not altered by ethanol or
KRG administration either, and plasma total cholesterol and LDL cholesterol levels were improved
when KRG 700 mg/kg were co-administered in thecurrent study (Fig. 2B). These plasma lipid patterns after alcohol consumption were very similar
to other’s six-week study results.33) However, Horieet al.34) reported that plasma triglyceride and total cholesterol concentrations increased after alco-

518

hol consumption. The partial inconsistancy between
peripheral and hepatic lipid concentrations in thecurrent study might be caused by the easily fluctuated biochemical characteristics of plasma, while
relatively stable characteristics of liver tissue. This
inconsistency could be corrected by prolongation of
the study period over two or three months, resulting
in more correlated and dose-dependent results between liver and plasma when administered ethanol
or KRG.35)
Nevertheless plasma lipid profiles were notdose-dependent to KRG co-administration, antihepatosteatotic effect of KRG on AFL rat model
was proved dose-dependently by the examinationsof liver lipid contents, histopathological findings,
liver to body weight and liver function tests. How
AFL could be improved by ingestion of KRG 700–
1400 mg/kg per day was not fully understood by
this study, however we referred that KRG prevented
or retarded alcoholic disruption of lipid metabolism
in livers, reflected by changes in the hepatic lipid,
possibly lipoproteins, metabolism such as impairment of transportation of lipoproteins,36) inhibitionof fatty acid oxidation,37) and enhancement of lipogenesis,38) as well as other toxic effects on hepatic function such as AST and ALT levels in plasmacaused by acetaldehyde.37) Energy intake39) andfatty acid composition of the diet40) could also influence the development of AFL, however energy
derived from ethanol in the diet were strictly controlled energy-proportionally by pair-fed matchingwith corn-starch among the groups in this study. Dietary energy inputs from polyunsaturated fatty acids
like corn oil and safflower oil were constant among
the groups at 8.5 and 2.7% of total energy intakes
respectively, and contributions of monounsaturated
fatty acids like olive oil were held at 28.4% of total
dietary input. These low compositions of polyunsaturated fatty acid consumption could not influence the induction of AFL. According to the control of energy intakes, body weight variations along
the time sequences were not significantly different among the ethanol-administered rats, however
naive rats were distinctly heavier than the ethanoladministered rats (Fig. 3A). This difference might
be caused by wasteful expenditure of energy underchronic consumption of alcohol, and by less effectively deposited energy as body mass from alcohol
than that from carbohydrate,41) resulting in impairment of lipid metabolism in livers.
Additionally, the dose of KRG 700–1400 mg/kg
for suppressing AFL in this study seemed quite

Vol. 57 (2011)high. However it is acceptable as a pharmacodynamic dose for animal studies when considered thata recommendation of Korea Ginseng Corporation
for KRG is 3 g/day for adults as a food supplementin Republic of Korea, and that KRG has relatively
small amount (about 70 mg/g of KRG) of saponin
which is a representative effective component. Besides, KRG was less toxic than fresh Korean ginseng.13, 14) In other studies, Kim and Park42) examined the effect of Panax ginseng extract in humans
at the high dose of 6 g/day for eight weeks without any reported toxicity. And Kwak et al.43) examined also the effect of high dose (100–1000 mg/kg)
of red ginseng acidic polysaccharide in a rat model,
resulting in significant anti-hyperlipidemic effect at1000 mg/kg dose.
In conclusion, co-administration of KRG significantly retarded development of AFL and prevented
development of early signs of the progression to cirrhosis at the oral dose of KRG 1400 mg/kg per day
for six weeks. To elucidate possible mechanisms
for the protective effects of KRG on steatosis, inflammation and fibrosis in the alcoholic liver disease, further studies are needed to examine hepaticfunction and toxicity by redox changes and oxidative stress with extended study period.
Acknowledgement This work was supported by
National Research Foundation of Korea Grant
funded by the Korean Government (KRF-2008-532C00041). And we would like to thank Professor
Seung-Ju Jekal for his support with evaluation ofhistopathological characteristics of liver tissues, andProfessor Eric B. Richardson for his sincere English
editing.

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