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ISBN 978-94-017-9657-6 ISBN 978-94-017-9658-3 (eBook)
DOI 10.1007/978-94-017-9658-3
Library of Congress Control Number: 2014958968
Springer Dordrecht Heidelberg New York London
© Springer Science+Business Media Dordrecht 2015
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Editors
Raymond Chuen-Chung Chang
Laboratory of Neurodegenerative Diseases
Department of Anatomy
LKS Faculty of Medicine the University
of Hong Kong
Hong Kong
China
Kwok-Fai So
Department of Anatomy
LKS Faculty of Medicine the University
of Hong Kong
Hong Kong
China
v
Preface
The fruit of Lycium barbarum (also called Wolfberry) is known to be anti-aging and
nurtures the eyes or vision. It is an upper class Chinese medicine, meaning that it can
be used as medicine for therapy as well as an ingredient in Chinese cuisine. Collective
efforts from different research teams have proven that the fruits of Lycium barbarum
have rich sources that protect our whole body, from the skin to the liver, brain and eyes.
Therefore, regular consumption of Lycium barbarum can help us to keep the balance
of Yin/Yang in our body to fight against any possible age-associated diseases.
There is a famous Chinese story related to Lycium barbarum. One day a young
man was walking in a village. On his way, he found two people arguing with each
other in a narrow lane. He went to see what had happened and found a relatively
young and strong man with black hair arguing with a weak elder with grey hair. It
looked like the elder had been blamed for something. In Chinese culture, we all
have great respect for the elderly. This was why this young man did not feel quite
right and thought that the man with black hair was not paying respect to his senior.
He asked this weak elder with grey hair whether the black-haired man had done him
some injustice. The grey-haired man then pointed to the strong black-haired man,
saying, ‘he is my big brother’. The strong black-haired big brother said that his little
brother did not listen to him and take Lycium barbarum. This was why his little
brother looked old and weak.
From this story, we have insight into the beneficial effects of Lycium barbarum.
In this book, we have carefully arranged the content from the plant, the chemical
components and the effects on different organs/biological systems as well as its
potential harmful effects. Authors in every chapter used different scientific methods
to prove the effects of Lycium barbarum. We are not just showing the benefits of Ly-
cium barbarum. Some people may be allergic to Lycium barbarum. This book is the
first book about Lycium barbarum written in English. As more people are searching
for health food supplements and there are many so-called ‘secrete formulations of
herbs and health food supplements’, we should look for some reliable health food
with solid scientific evidence and be cautious of any possible deleterious effects.
We hope that this book gives us a comprehensive understanding of the pros and
cons of this anti-aging Lycium barbarum.
Raymond Chuen-Chung Chang
Kwok-Fai SO
vii
Contents
1 Chemical and Genetic Diversity of Wolfberry ........................................ 1
Ying Wang, Hao Chen, Min Wu, Shaohua Zeng, Yongliang Liu
and Jingzhou Dong
2 Immunoregulation and Lycium Barbarum............................................... 27
Xiaorui Zhang, Wenxia Zhou and Yongxiang Zhang
3 The Antioxidant, Anti-inflammatory, and Antiapoptotic
Effects of Wolfberry in Fatty Liver Disease ............................................ 45
Jia Xiao and George L. Tipoe
4 Effects of Lycium barbarum on Modulation of Blood Vessel
and Hemodynamics .................................................................................... 65
Xue-Song Mi, Ruo-Jing Huang, Yong Ding, Raymond Chuen-Chung
Chang and Kwok-Fai So
5 Dermatologic Uses and Effects of Lycium Barbarum .............................. 79
Hui Zhao and Krzysztof Bojanowski
6 Lycium Barbarum and Tumors in the Gastrointestinal Tract ................ 85
Peifei Li, Bingxiu Xiao, Huilin Chen and Junming Guo
7 Prevention of Neurodegeneration for Alzheimer’s Disease by
Lycium barbarum ........................................................................................ 99
Yuen-Shan Ho, Xiao-ang Li, Clara Hiu-Ling Hung and Raymond
Chuen-Chung Chang
8 Prosexual Effects of Lycium Barbarum .................................................... 113
Benson Wui-Man Lau, Mason Chin-Pang Leung, Kai-Ting Po,
Raymond Chuen-Chung Chang and Kwok-Fai So
9 Lycium Barbarum: Neuroprotective Effects in Ischemic Stroke ............ 125
Amy CY Lo and Di Yang
10 Secondary Degeneration After Partial Optic Nerve Injury
and Possible Neuroprotective Effects of Lycium Barbarum
(Wolfberry) ............................................................................................... 135
Hong-Ying Li, Henry HL Chan, Patrick HW Chu,
Raymond Chuen-Chung Chang and Kwok-Fai So
11 Role of Lycium Barbarum Extracts in Retinal Diseases ........................ 153
María Benlloch, María Muriach, Gloria Castellano, Francisco Javier
Sancho-Pelluz, Emilio González-García, Miguel Flores-Bellver
and Francisco J. Romero
12 Allergenic Sensitisation Mediated by Wolfberry................................... 179
Jerónimo Carnés, Carlos H. de Larramendi, María Angeles
López-Matas, Angel Ferrer and Julio Huertas
viii Contents
79
Chapter 5
Dermatologic Uses and Effects
of Lycium Barbarum
Hui Zhao and Krzysztof Bojanowski
K. Bojanowski () · H. Zhao
Sunny BioDiscovery, Inc., 972 E. Main St., Santa Paula, CA 93060, USA
e-mail: kbojanowski@sunnybiodiscovery.com
Abstract Lycium barbarum (LB) is one of the most intriguing medicinal plants
in China. The beauty of its berries combined with the amount of beneficial effects
assigned to it would logically make it a strong candidate for skin use, yet rela-
tively few scientific publications address such application. Here, we will review the
skin-related effects of oral and topical preparations of LB, based on the published
scientific literature and work done in our own laboratory. We will also discuss the
obstacles and opportunities for LB in today’s dermatological field.
Keywords Wounds · Skin · Aging · Tightening · Wrinkles · Peptidoglycans
5.1 Skin Care
Skin is our largest and most conspicuous organ. It is also the only one, that humans
constantly expose to treatments not only to preserve its health, but also its beauty.
Historically, these treatments have been botanical in nature. In this respect, our
integumentary system is also unique—no other organ in the human body has been
target of so many botanical treatment modalities. Hundreds of plant extract com-
binations have been designed and applied to skin with expectations ranging from
the promise of eternal beauty to the cure of syphilis, leper, cancer, and other deadly
diseases. The purpose of the vast majority of these preparations is, however, some-
how more prosaic—to remedy various forms of inflammatory conditions (eczema,
psoriasis…) or to limit water loss by improving the barrier function of the skin.
Lycium barbarum (LB) is well positioned to provide both functionalities. With
respect to inflammation, it has been found in our and other laboratories that its fruits
(Wang et al. 2002; Chung et al. 2014), leaves (Dong et al. 2009), and bark (Zhang
et al. 2013) contain antioxidant components, which provide anti-inflammatory ac-
tivity, at least partially through the inhibition of the NF-κB signaling (Conner and
Grisham 1996; Oh et al. 2012). Animal studies linked this antioxidant activity to
a general senescence-inhibitory effect (as measured by a panel of oxidative stress
© Springer Science+Business Media Dordrecht 2015
R. C-C. Chang, K-F. So (eds.), Lycium Barbarum and Human Health,
DOI 10.1007/978-94-017-9658-3_5
80 H. Zhao and K. Bojanowski
parameters, motor skills, cognition, and nonenzymatic glycation level), bearing fur-
ther relevance to the antiaging skin care application (Deng et al. 2003; Li et al.
2007; Yi et al. 2013), in agreement with the free-radical theory of aging (Harman
2009).
The predominant LB components with antioxidant activity are peptidoglycans
(also called LB polysaccharides, or LBP) (Qiu et al., 2014 and Zhang, 1993); vita-
min B, C, taurine, and carotenoids in fruits; while flavonoids, such as rutin prevail
in the leaves (Jin et al. 2013). The seeds of Fructus lycii also contain oils, which not
only have antioxidant activity, but may improve skin barrier and decrease transepi-
thelial water loss through their ability to interact with the lipid matrix of stratum
corneum, such as it is the case of other bioactive oils (Tollesson and Frithz 1993).
LB oils may also provide vehicle function facilitating the intracellular absorption
of other bioactive components, such as carotenoids (as evidenced by the orange-
yellow color). A factor limiting the use of LB oils in cosmetics is the high extraction
cost due to low content (unlike peptidoglycans, which represent up to 40 % of the
fresh fruit pulp).
Despite the theoretically high potential for beneficial activity, there are only few
peer-reviewed studies specifically describing cutaneous benefits of LB. One of them
reports that ingesting the aqueous extract (juice) of LB protects mice from UV-in-
duced damage, such as inflammatory oedema, immunosuppression, and sunburn re-
actions (Reeve et al. 2010). Here also the antioxidant mechanism of action appears
to be implicated, as quantified by the inhibition of lipid peroxidation. This study
was tangentially corroborated by Wang and collaborators (2011), who reported that
pretreatment of human dermal fibroblasts with LBP prior to UVB irradiation saved
these cells from G1 growth arrest. Another report comes from our laboratory, where
LBP were applied topically on full thickness human skin explants with the result of
a selective metalloproteinase (MMP) inhibition. When one of these peptidoglycans
(LBGp5) was applied on fibroblasts cultured in suboptimal conditions, it was found
to stimulate the production of type I collagen and to promote cell viability (Zhao
et al. 2005). Interestingly, LBGp5 is the peptidoglycan with the highest antioxidant
activity among the five major LBPs (Huang et al. 2001). This report indicates that
the peptidoglycan fraction of LB has a beneficial effect on human skin when ap-
plied topically and warrants the development of LBP-based skin care products.
And yet, the Lycium barbarum-containing skin care formulations supported by
clinical studies are rare. One reason may be the presence of immunostimulatory
components in LB, which may be beneficial for fighting cancer (Tang et al. 2012),
but not necessary in skin care. The authors are not aware of any reports of skin re-
actions to topically applied LB, although allergy to ingested LB has been reported
(Monzón Ballarín et al. 2011; Larramendi et al. 2012) in individuals sensitive to
multiple food allergens, including tomato (there was cross-reactivity between lipid
transfer proteins of LB and tomato, which both belong to the same family—Sola-
nacea). Hence the importance of a careful, bioactivity-guided LB fractionation for
skin care applications.
Another reason for low skin care use of LB may be its regulatory status in some
countries, such as China and Japan, where this herb tends to be perceived as a
therapeutic modality and thus is not registered as a cosmetic ingredient. Because it
81
5 Dermatologic Uses and Effects of Lycium Barbarum
indeed has multiple therapeutic activities, one can say that LB is there a victim of its
own success. However, given its widespread dietary and even culinary use, regula-
tory restrictions specifically aimed at skin care formulations are nevertheless dis-
concerting. Furthermore, they cannot be substantiated by genotoxic concerns, since
LB was demonstrated to be genoprotective rather than genotoxic, using mitomycin
C-induced sister chromatid exchange (SCE) in lymphocytes and Ames methods.
Same study claimed that SCE in elderly (60 and over) patients ingesting LB poly-
saccharides was significantly ( p < 0.001) lower than in the same age control group
and became comparable with the SCE rate in young adults (Hong 1995).
In the US, where the topical use of LB is not restricted, two companies—Re-
sources of Nature (RON) and Grant Industries—appear to be leaders in LB ingre-
dient formulations. The clinically tested DC InstaliftTM Goji (RON, Fig. 5.1) and
Invisaskin GMTM (Grant Industries), which intelligently combine the physioco-
chemical and biological properties of LB peptidoglycans, have over 10 years (as of
2014) of history and underlie many finished skin care products with LB component.
5.2 Wound Healing
Given the above-mentioned beneficial effects of LB on human skin, we searched
and failed to locate any publications pertaining to the effect—whether positive or
negative—of this medicinal plant on wound healing. Therefore, we conducted a
3-day study on a partial thickness wound model in FT (full thickness) skin sub-
stitutes (MatTek, Ashland, MA), where the epidermal layer is peeled off and the
underlying dermal layer is exposed. The histochemical Masson trichrome stain
at day 3 (Fig. 5.2) shows that compared to the untreated control, the LBP-treated
Fig. 5.1 a, b Smoothing
effect of 3 % Instalift™ Goji
solution applied to mature
facial skin (a: time 0; b: time
60 min). Note the transfor-
mation in b of the initially
well-visible ( yellow arrows)
wrinkles in a. c, d Micro-
scopic image of the tighten-
ing effect of same solution
spread on glass slide ( left of
the meniscus line pointed by
black arrow), indicating the
possible mechanism of action
in vivo (mag.: ×40, c: time 0;
d: time 60 min). (Reprinted
with permission from RON)
82 H. Zhao and K. Bojanowski
wounds present a more advanced stage of healing. The difference with controls
consists in fibroblasts (dark purple stain), which appear to migrate upward provid-
ing topical coverage of the wound, while increasing the collagen output (the blue
stain) to facilitate this migration (Sunny BioDiscovery, Inc. unpublished results).
This is in agreement with the other two reports of the stimulatory effect of LBP on
human dermal fibroblasts (Zhao et al. 2005; Wang et al. 2011) and with the general
understanding of the role of the directional migration of fibroblasts during wound
healing (Song et al. 2013). However, there is no straight path to LBP-based wound
dressings. This is because LB peptidoglycans were reported to potentiate the effect
of warfarin—a blood thinner, raising concerns about the adverse effects on blood
coagulation (Lam et al. 2001; Ge et al. 2014). Interestingly, both coagulants and an-
ticoagulants have been reported to stimulate wound healing (Carney et al. 1992; Fan
et al. 2014) and whether LB interferes with this process in the absence of warfarin,
as well as the utility of LB in wound dressings remain to be discovered.
Conclusion
LB is a versatile medicinal herb with many health benefits and a few, mostly benign
side effects (such as temporary nosebleed following overconsumption (> 1 g) of
LBP). The dermatologic activities of LB are poorly understood, in part because of
the lack of motivation due to the regulatory constrains in Asian countries tradition-
ally utilizing this plant. We hope that this chapter conveys the potential of LB in
skin and wound care, and encourages more preclinical and clinical explorations in
this direction.
Acknowledgments We would like to thank Stephanie Ma for her expert assistance in this project
and George Majewski for helpful discussions.
Fig. 5.2 Effect of Lycium barbarum polysaccharides (LBP) on early-stage (day 3) wound heal-
ing in epidermis-stripped human skin substitutes (MatTek), as visualized by the trichrome stain
(mag. × 200). a Control (water); b LBP (500 μg/mL). Note more intense blue collagen stain and
more fibroblasts migrated upward to the wound bed in the LBP-treated tissue as compared with
the water control
83
5 Dermatologic Uses and Effects of Lycium Barbarum
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