An overview on panax ginseng (b.pharma project)

1. PROJECT REPORT
ON
“AN OVERVIEW ON PANAX GINSENG ”
DISSERTATION SUBMITTED TO
MANGALAYATAN UNIVESITY
DISSERTATION CARRIED OUT,
IN PARTIAL FULFILMENT FOR THE AWARD OF THE DEGREE OF
BACHELOR OF PHARMACY
SUPERVISED TO:
MISS. SUJATA KUMARI PROF.(DR.)DEV PRAKASH
M.PHARM Principal
ASSISTANT PROFESSOR (DEPARTMENT OF PHARMACY )
( 2018 -2022)
SUBMITTED BY
ANSHIKA MAHESHWARI
(20180310)
MANGALAYATAN UNIVERSITY
INSITITUTE OF BIOMEDICAL EDUCATION & RESEARCH
DEPARMENT OF PHARMACY
ALIGARH, UTTAR PRADESH

2. DECLARATION
I hereby declare that this project work “AN OVERVIEW ON PANAX GINSENG” is a
bonafide and genuine work carried out by us under the supervision and guidance of
PROF.(DR.) DEV PRAKASH and Miss. SUJATA KUMARI, Assistant professor &
Research Coordinator at Mangalayatan University, Aligarh, Uttar Pradesh. It is
further certified that no part of this work has been submitted either in part or full for the
award of any other degree/ diploma by me to this or any other university.
ANSHIKA MAHESHWARI
(20180310)
Date:
Place: Aligarh

3. CERTIFICATE OF SUPERVISOR
This is to certify that the thesis entitled “AN OVERVIEW ON PANAX GINSENG” is
submitted by Anshika Maheshwari partial fulfilment for the degree of B. Pharmacy. It is a
novel piece of work carried out by the candidate under my supervision. As of my knowledge, the
present study has so far not been submitted here and other University, for the award of degree.
PROF.(DR.) DEV PRAKASH
{Principal}
Date:- Miss. SUJATA KUMARI
(M.Pharm)
Assistant professor
{Department of pharmacy}
Place:- Aligarh

4. CERTIFICATE
This is to certify that this project work entitled “AN OVERVIEW ON PANAX
GINSENG” have been submitted by Anshika Maheshwari to the Mangalayatan University.
Date: Principal/Director

5. Evaluation Certificate
This is to certify that this dissertation has been evaluated.
Internal Examiner External Examiner
Signature
Name
Designation
Date
INDEX
S.No
Topic Page no.
1 Summary of panax ginseng 1 to 2
2 Introduction 3 to 4
3 History 5 to 6
4 History of ginseng of use 6 to 7
5 Pharmacological of ginseng use 8 to 9
6 Pharmacokinetics of ginseng 10 to 20
7 Recent Development 18
8 Conclusion 19
9 Reference 20 to 22

6. 1
AN OVERVIEW ON PANAX GINSENG
SUMMARY
The origin of ginseng dates back to prehistory. In China, Shennong also known as
“Emperor Yan” the “Yellow Emperor’’, or one of the “Three Emperors” (the Emperor
who is said to have started herbal medicine about 5,500 years ago) is reported to have
tasted hundreds of plants to discover many medicinal herbs. For many many years,
mankind hasbeen using various plants as nutrient, beverage, cosmetics, dye and medicine
to maintain health and to improve quality of life.
( Fig. N0.- 1 )
In Asia, particularly, Panax ginseng C.A. Meyer is considered to be the most precious
plant among herbs, and ginseng has been in the spotlight worldwide. Even in the Western
world, where there are greatly advanced research facilities and highly qualified man-
power available, and are regarded to be capable of conquering any hard-to-cure ailments,

7. 2
people has recently been reported to use herbal medicine, particularly ginseng. In the present
compilation of papers, many scientists contribute papers pertaining to “Chemo preventive effects
of ginseng”. In order to facilitate the readers understand easier and better, I catalogued this
collection as follows: The spiritual nature of ginseng in the Far East, the history of ginseng,
nomenclature and geographical distribution of ginseng, and type of ginseng products.

8. 3
Introduction :
Asian ginseng, commonly known as Korean ginseng (Panax ginseng C. A. Meyer), is a
perennial herb that has a long history worldwide as a medicinal herb (Kee 1999). The
main commercially valuable part is the ginseng root, which usually reaches a harvestable
stage after 4–6 years of growth. Ginseng has been valued by the Korean people as a
Traditional Medicine for atleast 2000 years. Korea began commercial cultivation of
ginseng in the 1900s, when the demand for ginseng was greater than the available supply
of wild plants (Kee 1999; Ang Leeet al. 2001). Several classes of compounds, including
triterpenesaponins, essential oils, polysaccharides, peptidoglycans, nitrogen-containing
compounds, and phenolic compounds (Tang and Eisenbrand 1992), have been isolated
from ginseng root since the beginning of the twenty century .Ginseng is one of the best-
known herbal medicines. It has been used widely in Korea, China, and Japan as a
restorative and antiaging agent in traditional medicine (Chevallier 2000;Kaufman et
al.

9. 4
2002; Kim et al. 2002; Xie et al. 2006). In the practice of traditional medicine, ginseng
root is considered the most valuable part of the plant. Ginsenosides, which have multiple
pharmacological effects (Attele et al. 1999; Xie et al. 2006), are the most useful and
beneficial constituents of ginseng roots. It has been reported that approximately 150
ginsenosides have been isolated from different parts of ginseng (Christensen and Steve
2008), with approximately 40 ginsenoside compounds identified in Panax ginseng alone.
Ginsenosides are distributed throughout the ginseng plant,but different parts of the plant
show distinct ginsenoside profiles and have different pharmacological activities (Atteleet
al. 1999). The key physiological effects of ginsenosides are their influence on central
nervous system (CNS) activity and their function as anticancer drugs (Shinkai et al.
1996;Yun 1996; Iishi et al. 1997; Kubo et al. 1992; Attele et al 2002; Dey et al. 2002).In
addition, ginsenosides are effectively used for their anticarcinogenic, anti-
inflammatory,antiatherosclerotic antihypertensive, antidiabetic, and antistress activity (Lu
et al. 2009). The effectiveness of ginseng continues to be disputed and debated. This
article reviews the history of ginseng and its traditional and modern pharmacological
uses. In this detailed review we will bring together traditional uses and modern
pharmacological uses and provide a foundation for a more rigorous systemic
investigation of ginseng.

10. 5
History of ginseng :
General history –
The name ginseng comes from the Chinese word Ren Shen, which literally means
Bhuman plant, mainly because ginseng roots often resemble the form of a man (Oxford
Dictionaries Online, s.v. B ginseng). The name also means B short person, because it
wasbelieved that an omnipotent spirit from the mountains sent this divine root in a human
form to liberate and rescue oppressed people. Generally, the originating area of ginseng is
known to be in Shang dang, China. The originating time, which has been estimated
according to textual and archeological outcomes, is known to be the first century B.C.,
during the Han dynasty era. This can be referred to as the ‘Chinese origin theory of
ginseng’. According to such hypothesis, the Chinese only discovered ginseng ‘suddenly’
during this time when it should have been self-generating for thousands of years before.
However, Shang dang has been one of the historic centers of China since the ancient
period and specially took prominence in terms of the beginning and development of
Chinese pharmaceutics. Moreover, there were six characters that expressed at the early
stage and were used together with each other up to the days of Ming and Qing dynasty.
Also, this theory did not explain clearly about the formation of ginseng character. Hence,
it is fairly obvious that the ‘Chinese origin theory of ginseng’ do not answer
appropriately

11. 6
To the fundamental questions of the origin of ginseng. In order to approach such mystery,
perspectives need to be newly shifted to the ‘outer origins’ of Chinese ginseng. In this
case, ‘outer’ only points to Manchuria and Korea, since these areas are the only
candidates regarding the natural circumstances of ginseng growth. So, it can be inferred
that ginseng has first been identified with the locals of Manchuria and Korea, and then
underwent influx to China to have been used as a medicinal stuff (Yang and Yeo 2004).
European botanists who were categorizing plants gave ginseng the name Panax, from the
Greek word Panacea, a universal, versatile remedy for every illness. It was probably first
used as a food, but records show that ginseng was also used for medicinal purposes more
than 3000 years ago. Control over ginseng fields in China and Korea became an issue in
the sixteenth century (Kim 2007). It has been reported in The Old Chinese Canon of
Medicine that ginseng could strengthen the soul, increase eye sight, help clear the heart,
remove evil, improve understanding, invigorate the body, and prolong life if taken for
long periods. One of the emperors in China mentioned that herbal medicine uses began
about 5500 years ago and reportedly tasted several plants and discovered many medicinal
herbs (Zheng 1985). The original work was lost longago, but studies by Shennong were
handed down verbally over many generations and were compiled into a commentary
book, ShennongBencao Jing, during the Liang Dynasty, 502 to 557 A.D. (Wang
1987).Ginseng was also mentioned in Jijuzhang in China between 48 and 33 B.C.
Ginseng was mentioned in writing in ShanghanLun for the prescriptions of Treatise on
Fevers, written between 196 and 200 A.D.

12. 7
History of ginseng use :
The use of Panax ginseng has a long and rich history both in TKM(Traditional Indian
medicine) and TCM (Traditional Chinese medicine)and has been traced back to the
Han Dynasty. Korean ginseng is one of the most widely used and acclaimed herbs in
the world. White ginseng is simply the dried or powdered root of Korean ginseng,
while red ginseng is the sameroot that is steamed and dried in heat or sunlight. Red
ginseng is said to be slightly stronger and more stimulating in the body than white,
according to Chinese herbalism. Korean ginseng has historically been one of the most
expensive of herbs, as it has been highly in demanded in China and the far East
centuries . Wild Korean ginseng is now nearly extinct from many regions. Single roots
of wild plants have recently have recently been auctioned in China and New York
City for sums approaching $50,000. Most of the world’s supply of Korean ginseng is
cultivated by farmers in Korea and China.

13. 8
Traditional use of ginseng:
Ginseng root has been utilized for many purposes since its introduction including
benefiting psychiatric and neurological conditions and enhancing vitality, especially by
the people of China, Japan, and Korea. Ginseng also has a long history in mythology,
(Fig no.- 2
herbalism, and medicine. Claims about its healing properties include the remedy of aging,
psychiatric problems, and internal organ dysfunction .
Pharmacological use of ginseng:
Though ginseng has been used for a long time, and its effectiveness is noted in the
ancient Chinese medicine, many of the mechanisms, constituents, and effects of ginseng
remain unknown. Since the twentieth century, researchers and scientists have tried to use
modern chemistry and pharmacology to study ginseng. The modern study of ginseng has
made great progress, and the general chemical constituents, pharmacological activities

14. 9
and therapeutic uses of ginseng have recently been defined. Recently researchers have
identify ginsenosides as the most active constituents of medicines made from ginseng.
To date, more than 40 different ginsenosides have been identified indifferent parts
of ginseng (Liu and Xiao 1992; Back et al. 1996). The principal constituent of ginseng is
ginsenoside which varies depending on Panax species, plant age,plant part, preservation
method, harvest season, and extraction method (Liberti and De Marderosian 1978;
Phillipson and Anderson 1984). Ginsenosides, many of which exist in minute amounts,
are unique to Panaxspecies and are supposed to be responsible for the effectiveness of
ginseng (Tyler 1993; Wakabayashiet al. 1997; Fleming 1998). Ginsenosides operate by
diverse mechanisms, with each having distinct and tissue- dependent effects (Murphy and
Lee 2002). The pharmacological activities of ginseng are summarized below. Ginseng
or ginsenosides have shown protective effects in various neurodegenerative diseases.
Ginseng is effective against Alzheimer’s and Parkinson disease and even Huntington’s
disease. Administration of a single oral dose and ginsenosides to amyloid precursor
protein transgenic mice reduced the level of amyloid beta(1–42) in mice brains
(Chenetal. 2006). Ginseng leaf extract is effective against CNS depression and also
showed neuroleptic effects in mice (Saito et al. 1973; Wang et al. 1982) extract of
ginseng had a positive response on the CNS (Deyamaand Najazawa 2001). Leaf extracts
of Siberian ginseng were found to have antifatigue, antistress, and antidepressive effects.
A Chinese herbal formula (named as Jiannaoning) prepare from ginseng leaf given to rats
with cerebral ischemia increased memory function(Song et al. 2006) and up regulated the
content of interleukin-2, interleukin-6, and neuropeptide Y in rat brains. Diabetic patients
have a higher incidence of cardiovascular disease in part because of poorly controlled
hyperglycemia. Reports of the effects of ginseng on sides glycemic control are large
anecdotal. Ginseng given to mice as a treatment for diabetes lowered postprandial

15. 10
glycemia in type II diabetics (Vuksan et al. 2001; Quan et al 2012)
Pharmacokinetics of ginseng :
Various in vivo and clinical study have identified the pharmacokinetics of various
ginseng spanish compound however, The pharmacokinetics activities of ginseng and
ginsengonsides are still not clearly understood because of their heterogeneous and
diversified chemical structures. Studies have revealed that absorption of ginseng saponins
is low when they are administerd orally ; they have low membrane permeability and are
extensively metabolized 113 in the gastro intestinal tract. Ginsenosides Ra3,Rb1,Rd,Rg3
and Rh2 saponins show better 114 bio availbility than ginsenosides Ra3,Rb1,Rd,Rg3 and
Rh2 saponin. In human ,the half 115 lives (T1/2) of saponins are usually less than 24
hours. Possible drugs 116 interactions have been reported between P.ginseng and
warfarin , phenelzine and alcohol Potential pharmacological uses of ginseng .
Potential pharmacological uses of ginseng :
(1) Antioxidant activity : Free radicals, reactive oxygen species (ROS), and reactive
nitrogen species (RNS) originate from both exogenous and endogenous sources. Major
exogenous sources are pollution,alcohol ,tobacoo consumption smoking.heavy metal
,transition metals ,industrial solvent ,pesticides and certain drugs like halothane
,paracetamol , and radiation .

16. 11
(1) Anti-inflammatory activity :
Inflammation is a normal response to infection that involves both the innate and adaptive
immune systems. Heat, pain, redness, swelling, and loss of function are the cardinal features of
inflammation . A number of in vitro, in vivo, and clinical studies suggest that ginseng has some
degree of anti-inflammatory activity .
( Fig.no.- 3)

17. 12
(2) Anti-cardiovascular disease activity:
Cardiovascular disease (CVD) comprises a range of conditions involving the heart or blood
vessels and is one of the leading causes of death around the globe . Active components of
ginseng can stimulate nitric oxide (NO) production, inhibit ROS production, increase blood
circulation, and help in adjusting lipid profiles . In the cardiovascular system, calcium ions
(Ca2+ 190 ) play a critical role in the regulation of contraction and intracellular signaling, which
are vital for heart function . Different studies have revealed that ginsenosides can inhibit Ca2+
192 entry, and thus improve cardiac functions . One in vivo study showed that ginsenoside Rb1
can inhibit cardiac hypertrophy in a rat model . Studies showedthat P. ginseng can help maintain
proper blood circulation and can boost vascular endothelial cell-derived NO secretion, which
decreases blood pressure . Other studies have reported that the components of ginseng also
function as anticoagulation agents in the circulatory system (Table S6). In vitro as well as in vivo
studies have demonstrated that ginsenosides Rg1, Rg3, and water extract of KRG suppressed
platelet aggregation by down regulating thrombin- enhanced fibrinogen binding and P-selectin
expression via downstream signaling elements, e.g., CAMP and ERK2, in addition to the release
of 1,2-diacylglycerol . The n-butanol extract (NE3) and saponins from P. noto ginseng as well as
radix noto ginseng have been shown to regulate total cholesterol (TC), TG, and LDL-C levels
based on in vivo experiments.

18. 13
(3) Anti-obesity :
Obesity is one of the major public health problems in the modern age. Obesity is associated with
major no communicable diseases such as coronary heart disease, diabetes mellitus, cancer, and
sleep-breathing disorders . Unfortunately, drugs that are used in the treatment of obesity have
major side-effects. Alternative medicines for reducing weight are therefore of great interest.
Studies, including clinical studies, have reported that ginseng has an anti- obesogenic effect but
the anti-obesity mechanisms of ginseng have not been clearly elucidated . In vitro and in vivo
studies have suggested that ginsenosides have the potential to increase energy expenditure by
stimulating the adenosine monophosphate activated kinase pathway, and are capable of reducing
energyintake in a similar way. Kim and his team reported that serum levels of TC, TAG, and
LDL decreased while those of high-density lipoprotein (HDL) increasedafter the administration
of giinseng extract for 8 weeks. However, the study had several limitations.
(Fig.no.4)

19. 14
(4) Anti-diabetes effect :
Diabetes mellitus (DM) is a metabolic condition that impairs the ability of the body to process
blood glucose due to defects in insulin secretion, insulin action, or both. There are two major
categories of DM: type 1 diabetes mellitus (T1DM), commonly known as insulin dependent
DM, and type 2 diabetes mellitus (T2DM), commonly known as non-insulin dependent DM.
Ginseng is used as a traditional medicine for treating DM in China Korea, and Japan Yun and
his team investigated the anti-diabetic effects of wild ginseng ethanol extract (WGEE) on high-
fat diet-induced ICR mice for 8 weeks. WGEE significantly reduced fasting blood glucose in a
dose-dependent manner. Different in vitro and in vivo studies have shown thatCompound K, an
active metabolite of ginsenosides, can stimulate insulin secretion by primary cultured islets .
Compound K enhanced insulin secretion in a concentration-dependent manner through K-
channel dependent pathways. Vuksan and his team examined the clinical efficacy of KRG in 19
participants with well-controlled type 2 diabetes, and after 12 weeks of supplementation, found
that it improved glucose and insulin regulation.

20. 15
(5) Anti-central nervous system (CNS) disorder effect :
Disorder and affects CNS motor/ function. The exact cause of PD is not clear, but different studies
have suggested that both genetic abnd non-genetic factors such as environmental factors play a
pivotal role in disease progression. Oxi dative stress, mitochondrial dysfunction, and protein
mishandling are all thought to be involved in PD pathogenesis. Due to cell death in the substantia
nigra, dopamine expression decreases, resulting in classical motor symptoms in an affected person.
Lewybodies and loss of dopaminergic neurons in the substantia nigra are commonattributes of PD
Recent studies reported that ROS, high reactive iron levels, and an impaired antioxidant defense
system can cause neural degeneration. A number of studies have showed that the ginsenosides
Rb1, Rg1, and Rd can exert neuro protective effects by inhibiting oxidative stress and neuro
inflammation. These ginsenosides also decrease toxin-induced apoptosis. An in vivo study reported
that Rg1 protected against MPTP-induced apoptosis in substantia nigra neurons by decreasing
levels of cleaved caspase-3, Bax, and INOS, and increasing levels of Bcl-2 and Bcl-xl. However,
total ginsenosides were found to exert an anti-epileptic effect by inhibiting KA-induced
synaptosomal oxidative stress related to hippocampal de generation via activation of adenosine
A2A receptors . In vivo experiments revealed that ginsenoside Rd can play a protective role in
cerebral ischemia by upregulating ERK1/2 and PI3K/Akt signaling pathways. Another
ginsenoside, Rg3, improved learning and memory impairments in lipopolysaccharide-induced
cognitively impaired mice. A clinical study was conducted among patients with AD in the
Department of Neurology at the Clinical Research Institute in South Korea, and the results
suggested that taking ginseng root daily for 12 weeks improved mental performance significantly.

21. 18
Commercial ginseng products :
South Korea, China, Canada, and the US are the main producers of ginseng and the total
production of fresh ginseng is about 79,769 tons. The world ginseng market, including ginseng
root and processed products, is estimated to be worth $2,084 million (USD). Ginseng is
distributed in 35 countries around the globe and among them, 19 countries including South
Korea and China are both importers and exporters. People use different types of commercial
ginseng products . Great technical progress has been made in the extraction of Rg1, Re, Rh2, and
Rg3 with yields up to several kilograms. However, this is not enough to meet the demand, and
newer synthesis methods need to be developed to meet industrial production requirements.
(Fig no.- 5)

22. 17
Ginseng toxicity:
As an herbal medication as well as dietary supplement, ginseng and ginseng products have been
well studied. The Web of Science had a total of 3,974 records for P. ginseng research from 1959
to 2016 published by authors from 64 countries Nevertheless, to the best of our knowledge, there
are a limited number of studies regarding ginseng toxicity; most of these studies have focused on
ginseng abuse or misuse. Some case studies reported that ginseng exerted a toxic effect on
humans regardless of gender and age. Examples of toxic or adverse effects caused by ginseng
abuse or misuse include maniac episodes, uterine bleeding, gynecomastia, long QT syndrome,
atrial fibrillation with bradycardia, hypertensive crisis, and acute lobular hepatitis . Ethanol-
extracted ginseng can cause cerebral arteritis, and ginseng is one of the causes of
Stevens- Johnson syndrome. A recent study also claimed the occurrence of cutaneous adverse
effects in a 60-year-old woman, i.e., inflammatory papules due to consumption of ginseng . A
more recent study reported that standardized p. ginseng extract, depending on dose and usage
duration, can affect cardiac function by causing heart failure, decreasing blood pressure, and
causing diastolic dysfunction .Further more, a few studies raised the concern that interactions
between ginseng and other drugs might be hazardous for health, especially in patients taking
warfarin to prevent fatal strokes and thromboembolism. Ginseng consumption during the first
trimester of pregnancy and lactation may also have a toxic effect, and this herb should be taken
with caution by pregnant women.. A substantial amount of research is required to determine the
safety profile of ginseng and its active ingredients.

23. 18
Recent developments:
The past decade has seen the development of ginseng based nanoparticles and nano composite
technologies . A study in 2019 reported delivery of ginsenoside Rb1 from P. notoginseng using
chitosan/alginate nano composite film; the rate of ginsenoside Rb1 liberation from that
composite films was ‘proportional to the increase in pH solution and inversely proportional to
the content of loaded ginsenoside (Rb1). Another study in 2018 claimed that direct conjugation
of superparamagnetic iron oxide nanoparticles (SPIONs), Compound K, and ginsenoside Rg3 in
lipopolysaccharide-induced RAW 264.7 cells diminished nitric oxide and inducible nitric oxide
synthase (INOS) activity depending on the doses administered.

24. 19
Conclusions : There is great interest in pharmacological agents from natural sources that
have predictable health benefits against inflammation, oxidative stress, microbial infection,
cancer, diabetes, sexuality problem, central nervous system disorders, and cardiovascular
disorders with no toxicity property as summarized. However, the job of discovering new ginseng
constituents is still underway. Ginseng is distributed in 35 countries around the globe and the
ginseng market is estimated to be worth $2,084 million. The pharmaceutical industry is a rapidly
growing industry; in 2014, global pharmaceutical revenues had surpassed one trillion dollar
benchmark. Traditional herbs are a great source of therapeutic agents, for example artemisinin
from Artemisia annua. Several studies have revealed that ginsenosides and their derivatives have
great pharmaceutical potential to prevent and treat different diseases. We strongly believe that
traditional herbs will open up new horizons for the pharmaceutical industry in the future.
Governments, health care agencies, and R&D groups of different pharmaceutical industries
could benefit from focusing on ginseng research

25. 20
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