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Lung Cancer Activity of Caralluma Species, an Overview

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Genus Caralluma a perineal herb of Asclepiadaceae family, it is used as traditional medicine for the treatment number of diseases like diabetes, inflammation, leprosy, obesity, rheumatism, diseases of the blood helminthic diseases, stomach disorders, abdominal pains, septics, chronic lung diseases, such as tuberculosis and cancer. We focus critical evaluation of genus Caralluma use in the lung cancer treatment in this review.
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Citation: Kommidi DR, Koorbanally NA and Moodley B. Lung Cancer Activity of Caralluma Species, an Overview.
Austin J Lung Cancer Res. 2016; 1(2): 1006.
Austin J Lung Cancer Res - Volume 1 Issue 2 - 2016
Submit your Manuscript | www.austinpublishinggroup.com
Kommidi et al. © All rights are reserved
Austin Journal of Lung Cancer Research
Open Access
Abstract
Genus Caralluma a perineal herb of Asclepiadaceae family, it is used
as traditional medicine for the treatment number of diseases like diabetes,
inammation, leprosy, obesity, rheumatism, diseases of the blood helminthic
diseases, stomach disorders, abdominal pains, septics, chronic lung diseases,
such as tuberculosis and cancer. We focus critical evaluation of genus Caralluma
use in the lung cancer treatment in this review.
Keywords: Caralluma; NSCLC; SCLC; Radiotheraphy
cancer activity.
Types of Lung Cancer
Lung cancers are of three types, knowing the type of cancer really
aects the treatment options and diagnosis.
Non-Small cell lung cancer
Non-Small Cell Lung Cancer is the most common type of lung
cancer, among all lung cancers 85% of cases are Non-Small Cell Lung
Cancers (NSCLC). NSCLC is further subdivided into Squamous
Cell Carcinoma, adenocarcinoma and large cell carcinoma. e cells
dier in size and shape and chemical makeup when looked under the
microscope in these subtypes.
Squamous cell carcinoma: Squamous cell carcinoma is also
known as epidermoid carcinoma; about 25-30% of NSCLC is
squamous cell carcinoma. It starts in the at squamous cell that is
lined in the airways of the lungs, squamous cell carcinoma is oen
linked to smoking, and these are usually located in the large bronchi
that join the trachea to the lung. A Continuous cough with blood,
out of breath, fatigue, discomfort when swallowing, chest pain, fever,
hoarseness, weight loss and poor appetite, are the common signs and
symptoms. Individuals experience hypocalcaemia which results in
muscle weakness; Obstruction of the airway may lead to pneumonia
and atelectasis. Squamous Cell carcinoma can be diagnosed through
chest CT scan, sputum cytology, brocho scopy, PET scan and
Endobronchial Ultrasound.
Adenocarcinoma: Lung adenocarcinoma is mostly seen in
women in particular below 45 years of age and especially in Asians, it
may be in lungs before its detection and diagnosis. It usually begins
in the tissue in the outer parts of the lungs, and it is oen found in
non-smokers. Early symptoms of the lung adenocarcinoma are
fatigue, mild shortness of breath, in its later stages a chronic cough
and coughing of up the blood can be seen, it is diagnosed by chest CT
scan, sputum cytology, brochoscopy and PET scan.
Large cell carcinoma: Large cell carcinoma of lungs originates
from the transformed epithelial cells, it’s a heterogeneous
undierentiated neoplasm, and it starts in the central part of the lung;
this is usually discovered in the later stages. LCLC tend to grow quickly
and of all lung cancers it comprises 5%-10%. e Previous history
of smoking makes the LCLC more risky (2.3%) compared to non-
smokers. Cigarette smoking is the predominant reason for the LCLC.
Introduction
Lung cancer
Uncontrolled cell division that spreads throughout the body is
cancer; it’s a group of diseases which can lead to death if not controlled.
External factors (tobacco, infectious organisms, and unhealthy
diet) and internal factors (inherited genetic mutations, hormones,
and immune conditions) are the main causes of cancer. ese i.e.
external and internal may act composed or in order resulting cancer,
it may pass a decade from exposure to detection of cancer. Among
all types of cancers lung and breast cancers are most diagnosed and
leading cause of deaths in men and women. WHO report states
that the common causes of cancer deaths are cancers of lung (1.59
million deaths), liver (745 000 deaths), stomach (723 000 deaths),
colorectal (694 000 deaths), breast (521 000 deaths), oesophageal
cancer (400 000 deaths) [1]. Mainly cancer arises from the interaction
of person’s genetic factors and three types of external factors like
physical carcinogens (Ultraviolet and Ionizing radiation), chemical
carcinogens (Tobacco, asbestos, smoke, aatoxin, and arsenic) and
biological carcinogens (virus, bacteria and parasites). e incidence
of cancer is more in developed nations than less developed nations
but mortality is more (65%) in less developed nations. Prostate cancer
in men and lung cancer in women is leading death cause of cancer in
more developed Nations, the burden of cancer is slowly shiing to less
developed Nations due to the aging of the population and increasing
pervasiveness. e genus Caralluma of Asclepiadaceae comprises of
approximately 350 species all around the globe. Genus Caralluma
normally prefers a dry habitat and decay when they are exposed to an
excess of water. e support may be necessary, as they do not contain
brous tissue. Some of the plants grow even up to a height of 100 cm
under protection [2]. Review of literature revealed medicinal uses of
genus Caralluma [3-9]. e distribution of Carallumas ranges from
the Mediterranean to East Indies, mostly found in Southern Europe,
Iran, Iraq, African countries like Kenya, Somalia, Sudan and Ethiopia,
Arabian countries like Oman, UAE and Yemen and Asian countries
like Afghanistan, Pakistan, India, Nepal, Burma and Sri Lanka [10].
Methodology
e data in the present review is retrieved from the published
papers through online bibliographic databases: Google Scholar, ISI
Web of Knowledge and Science Direct Navigator. ere are a number
of publications on caralluma but we considered the ones with lung
Review Article
Lung Cancer Activity of Caralluma Species, an Overview
Devendar Reddy Kommidi*, Neil A Koorbanally
and Brenda Moodley
School of Chemistry and Physics, University of KwaZulu-
Natal, South Africa
*Corresponding author: Devendar Reddy Kommidi,
School of Chemistry and Physics, University of KwaZulu-
Natal, Westville, Durban, South Africa
Received: December 23, 2015; Accepted: January 28,
2016; Published: February 24, 2016
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WHO has further sub dived LCLC into Giantcell carcinoma, Basaloid
large cell carcinoma, Clear cell carcinoma, Lymphoepithelioma-like
carcinoma, Large-cell lung carcinoma with rhabdoid phenotype and
Large cell neuroendocrine carcinoma; non-productive cough and
weight loss are the signs and symptoms of the LCLC. is type of
lung cancer may spread to nearby lymph nodes and chest wall. LCLC
is diagnosed through CT, MRI and PET scans, biopsy and sputum
cytology, apart for these tests thoracentesis, mediastinoscopy, needle
biopsy, bronchoscopy, Video Assisted oracoscopic Surgery (VATS)
and surgery is also done for the prognosis of LCLC. ese subtypes
of NSCLC are grouped together for the treatment and diagnosis are
oen same.
Small cell lung cancer
Small Cell Lung Cancer is a disease in which malignant cell form
tissues of the lung. ere are two types of small cell lung cancers;
these two types include a much dierent type of cells the cancer cells
of each type grow and spread in a dierent way. e sub types of
SCLC are named aer the cells found in cancer; these are Small Cell
Carcinoma and Combined Small Cell carcinoma. Smokings, being
exposed to second-hand smoke, family history with lung cancer,
treated with radiotherapy for breast or chest cancer, exposure to
asbestos, air pollution are the risk factors of SCLC. Chest discomfort,
continuous cough, trouble in breathing, wheezing, and blood in
sputum, hoarseness, trouble in swallowing, loss of appetite, weight
loss, tiredness and swelling in the face or veins of the neck are the
signs and symptoms of the SCLC.
Lung carcinoid tumour
Tumours are grown slowly and are rarely spread in lung carcinoid
tumour; these are fewer than 5% in lung cancers. Lung carcinoid
tumour is also known as neuroendocrine tumors. ere are four types
of tumours namely small cell lung cancer, large cell neuroendocrine
carcinoma, atypical carcinoid tumour and typical carcinoid tumour.
A Bloody cough, wheezing, shortness of breath and chest pain when
taking deep breath. Lung carcinoid tumour can be diagnosed through
Chest X-Ray, CT scan, Radionuclide scans, Sputum cytology, Biopsy,
Bronchoscopy and biopsy Endobronchial Ultrasonography (EBUS)
and biopsy, Needle biopsies, Surgical biopsies, Blood and Urine tests
and Pulmonary function tests.
Treatments Available
ere are dierent types of treatments are available for lung
cancer, the type of treatment varies with the type of lung cancer.
Chemotherapy
Powerful medication to kill cancer is chemotherapy; it can
be given in many ways. Chemotherapy is given before and aer
the surgery; medication before the surgery minimizes the size of
a tumour and increases the success rate of surgery. On the other
hand, the medication aer the surgery to prevents the return of
cancer. Chemotherapy also slows down the symptoms and prevents
the spread. It is used in the treatment of small cell lung cancers;
tumour usually spread to lymph nodes at the time of diagnosis in
small cell lung cancers, so chemotherapy is used instead of surgery,
chemotherapy is oen combined with radiotherapy, and usually it is
give in cycles.
Radiotherapy
Pulses of radiation are used to treat this type of treatment. Radical
radiotherapy which is also known as intensive radiotherapy is used
to treat patients suering from non-small cell lung cancer those
who cannot bare surgery. Stereotactic radiation is used for small
tumours instead of surgery. Palliative radiotherapy is used to control
symptoms and slowdown the spread of cancer, Prophylactic Cranial
radiotherapy (PCI) is used to stop the spread of small cell lung cancer
to the brain. Broadly there are three ways that radiotherapy is given
namely, conventional external beam radiotherapy, stereotactic
radiotherapy and internal radiotherapy.
Conventional external beam radiotherapy: In this type beams
are directed to the aected parts of the body using a machine.
Stereotactic radiotherapy: In this type accurate high energy
beams are used to deliver the higher dose of radiation to the tumour.
Surrounding healthy tissue is spared as much as possible
Internal radiotherapy: Tumour aected area is treated by
inserting a thin catheter (tube) consisting small amount of radioactive
material. is thin tube is removed aer some time. External
radiotherapy is mostly used in the treatment of lung cancer.
Surgery
ere are three types of surgeries to treat lung cancer namely,
Lobectomy, Pneumonectomy, Segmentectomy
Lobectomy: Lobectomy is suggested when cancer is in one section
of the lung, in this case one are more parts of the lung are removed.
Pneumonectomy: is type of treatment is ideal when the cancer
is located in the middle of the lung of has spread throughout the lung,
entire lung is removed in this case.
Segmentectomy: Segmentectomy is used when the cancer is
small and limited to one area of the lung. is type of treatment is
suitable for a limited number of patients.
ere is a general misconception that people whose lung is
removed cannot breathe properly, but that’s not true even aer
surgery they can normally breathe. Apart from all these, there are
much other treatment available for the lung cancer like biological
therapies, radiofrequency ablation, cryotheraphy and photodynamic
therapy.
Shortcomings of the treatments available
Body’s reaction to the cancer treatment depends on various
factors like, duration of the treatment, dosage and patients personal
history. ese side eects may be of short term or long term; mostly
side eects are short term and are painful and uncomfortable. e
possible side eects of the treatments available are blood clots, bone
issues, chemo brain, dental issues, diarrhoea, fatigue, lymphedema,
mouth sores, nausea and vomiting, neuropathy, pain rash and weight
loss or gain.
Chemotherapy side eects: Drugs are given to control quick cell
division in chemotherapy, but the cells of hair, skin, nails, sidelining
of the digestive system and blood cells also divide quickly, so these
cells also are aected by the chemotherapy. Some of the common side
eects are low blood cell levels, fatigue, nausea, mouth ulcers and hair
loss.
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Radiotherapy side eects: A side eect of radiotherapy depends
on the duration of the treatment, generally the treatment for few
weeks usually give more side eects than treatment for few days.
General side eects of radiotherapy are tiredness, sore throat, cough,
Figure 1: (A) Effect of cRL on lung cancer cell lines. The lung cancer cell
lines A-549 and H-460 were treated with different concentrations of cRL for
24 h, and the cell viability was measured by MTT assay. Each data point
represents the mean for four wells from three independent experiments
(mean ± S.E.). (B) cRL-induced clonogenic inhibition in lung cancer cells.
Lung cancer cells treated with different concentrations of cRL (0–300 ng/ml)
and clonogenic inhibition assays were performed in these cells. Cell survival
curve of lung cancer cells with treatments as assayed by colony forming
ability. The data shown are representative of the combined mean of three
independent experiments. (C) cRL-induced apoptosis in lung cancer cell
lines. Cells were treated with either 30μg/ml (A-549) or 40μg/ml (H-460 or
BEAS-2B) of cRL dissolved in DMSO and apoptotic assays were performed
at 6, 12, 24 and 48 h. Bar graph shows the percentage of apoptotic cells. The
base-line apoptosis in the untreated group was normalised with data on the
treated group. Each data point represents the mean of three independent
xperiments (mean±S.E.) (Rama S Ranga et al).
Figure 2: (A) Regulation of apoptotic gene expression by cRL. Whole cell
protein extracts were prepared from A-549 cells that were either left untreated
or treated with cRL for the time intervals indicated. The blot was probed with
antibodies for p53, Bcl-2, Bax and β-actin. (B) Effect of cRL on the localization
of p53 in lung cancer cell lines. Indirect immunouorescence analysis for p53
in A-549 and H-460 lung cancer cell lines following 24 h treatment with cRL.
The superimposed images show the cells undergoing apoptosis (Rama S
Ranga et al).
Figure 3: (A) Radio-sensitisation effect of cRL on lung cancer cell lines. The
cells (A-549 and H-460) were treated either with radiation alone or radiation in
combination with various concentrations of cRL for 24 h, and the cell viability
was measured by MTT assay. Each data point represents the mean for four
wells from three independent experiments (mean ± S.E.). Enhancement of
radiation-induced apoptosis in lung cancer cells by cRL. (B) A-549; (C) H-460.
Cells were treated with radiation alone (5 Gy) or radiation combined with cRL
(A-549; 15μg/ml; H-460; 20μg/ml) and apoptotic assay was performed after
24 h of exposure. Each data point represents the mean of three independent
experiments (mean ± S.E.) (Rama S Ranga et al).
Figure 4: Induction of caspase-3 activation in lung cancer cell lines. (A)
A-549; (B) H-460. Cells were left untreated or treated with cRL, radiation or
the two in combination and caspase activity was determined after 3, 6, 12
and 24 h. Caspase activities are expressed as the percentage of caspase
activity as compared to control and presented as mean ± S.E. of two samples
in triplicates (Rama S. Ranga et al).
Figure 5: Concentration of Methanolic Extraxt on X-axis (µg/ml).
MTT assay on A-549 cancer cell line on Y axis (Priya et al.).
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Figure 6: A-549 treated with 6.25µg/ml of Methanolic extract of C. mbriata
(Priya et al.).
Figure 7: A-549 treated with 12.5µg/ml of methanolic extract of C.mbriata
(Priya et al.).
Figure 8: A-549 treated with 25µg/ml of extract. A-549 treated with 50µg/ml
of extract (Priya et al.).
Figure 9: Treatment of cells for 24 hours with the crude extract of Caralluma
tuberculata over a range of concentrations. Cell growth was measured using
the NRU assay (Abdul Waheed et al).
hair loss, chest pain, temperature and shivering, feeling sick and sore
skin in the treatment area. Long-term side eects may develop aer
the completion of the prolonged treatment this is because of brosis;
brous tissue is less stretchy than normal tissue so breathlessness,
diculty in swallowing and heart problems may develop.
Radiotherapy to control symptoms is unlikely to develop side eects.
Advantages of traditional medicine for the lung cancer
Plants or mixture of plant extracts are used in herbal or traditional
medicine, this is a whole approach which includes physical, mental
and emotional wellbeing of the patients, it restores patients’ body
ability to protect and regulate itself. ere are dierent types of
traditional approaches for the lung cancer treatment namely, Western
herbal medicine, Chinese herbal medicine, Tibetan herbal medicine
and Ayurvedic medicine (Indian). e survival rate of the standard
treatments tending the patients to go for the traditional medicine
[11]. Western herbal medicine concentrates on the person (family
history, diet and lifestyle) rather than illness, Chinese herbal system
is called Traditional Chinese Medicine (TCM), this aims to restore
the ow of energy into the body that is known as QI (Chee). TCM
includes herbal medicine, acupuncture, massage therapy, traditional
breathing and movement exercise called qi gong (Pronounced as
Chee gong) and movement exercise called tai chi (pronounced as
tie chee). In TCM along with plant material minerals and animal
products are also being used [11]. e present review concentrates on
Indian traditional medicine (Ayurveda) limiting to genus Caralluma.
Ayurveda is the ancient Indian system of medicine which makes use
of inherent power of herbs, few herbs like curcuma longa, Withania
somnifera, Giloy, Commiphora Mukul, Bambusa arudinasea, Piper
longum, Vasaka and Ocimum tenuiorum are used in the cancer
treatment [12] (Figure 1-4).
Caralluma for the Treatment of Lung Cancer
Genus Caralluma reported to have many medicinal uses; here we
discuss the use of caralluma species for the lung cancer treatment.
C. negevensis is reported to be useful in the chronic lung disease like
cancer in Spain. Among the twenty new pregnane glycosides isolated,
compound seven reported to exhibiting anti-lung cancer activity [13].
Methanolic extract of the C.mbriata wall. Reported to exhibit anti-
lung cancer activity, Priya and his co-workers carried out cell viability
Figure 10: Treatment of cancer cells for 48 hours with specic organic
fractions of Caralluma tuberculata at 200 µg/ml. Cell growth was measured
using the NRU assay (Abdul Waheed et al).
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and growth inhibition activity of the methanolic extract of C.mbriata
Wall against A-549 lung cancer cell lines. Cytotoxic activity was
determined by Cell viability and cell morphology was observed under
the inverted microscope. e methanolic extract decreased the cell
viability and increased growth inhibition, results demonstrated that
the methanolic extract of C.mbriata had potential agent against
lung cancer, MTT assay was used for the anticancer activity of the
methanolic extract. [Rajaram] (Figure 5-12).
Concluding Remarks and Perspectives
Finally it is concluded that genus caralluma can be used as
Figure 11: Treatment of cancer cells for 48 hours pregnane glycoside over a
concentration range. Cell growth was measured using the NRU assay (Abdul
Waheed et al).
Figure 12: Treatment of cancer cells for 48 hours androstan glycoside over a
concentration range. Cell growth was measured using the NRU assay (Abdul
Waheed et al).
alternative medicine in the treatment of lung cancer as most of the
present treatments have side eects, establishment of signalling
pathway for the lung cancer treatment using caralluma is encouraged.
e alternative medicine can be used eectively if proper research is
done so the research in this direction is encouraging.
Acknowledgement
e authors are grateful to the School of Chemistry and Physics,
College of Agriculture, Engineering and Science, University of
KwaZulu-Natal, Westville, Durban, South Africa for funding and
research facilities.
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Citation: Kommidi DR, Koorbanally NA and Moodley B. Lung Cancer Activity of Caralluma Species, an Overview.
Austin J Lung Cancer Res. 2016; 1(2): 1006.
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Kommidi et al. © All rights are reserved
... While all other analytical grade chemicals: acetic acid, ethanol, methanol sodium nitrite, sodium hydroxide, ammonium thiocyanate, ferrous chloride, anhydrous are required for the action of ribonucleoside diphosphate reductase and eventually causes cellular toxicity (Al-Faifi et al., 2016). Antioxidants acts against the fabrication of free radicals through various possible ways, either by the inhibition of certain enzyme or chelation of metal ions like iron and copper etc., scavenging to reactive nitrogen (RNS) and reactive oxygen species (ROS) (Uttaraet al., 2009;Jyoti et al., 2015;Kommidi et al., 2016). In this way, antioxidants act as safeguard against oxidative damage and prevent life from various life-threatening diseases (Liede-Schumann et al., 2005). ...
... All the members Caralluma family are rich in pregnane, that is naturally conjugated with glycoside. These molecules appear as potential lead for drug development especially against cancer, hepatitis and diabetes (Deepak et al., 1998;Al-Faifi et al., 2016;Kommidi et al., 2016). Pregnane glycosides series have been extracted from its organic extracts that explicit cytotoxic effect on cell line of human diploid embryonic cell like MRC5 ( Abdel-Sattar et al., 2008;Abdel-Sattar et al., 2011). ...
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 Representatives of nearly all genera of the taxon-rich stem-succulent stapeliads and most of the few related, leafy genera were analyzed. Sequence data from two non-coding molecular markers (ITS region of nrDNA and trnT-L and trnL-F spacers as well as the trnL intron of cpDNA) support the traditional tribal affiliation of the genera, which form a monophyletic group. This monophylum breaks into a basal Neoschumannia/Anisotoma/Riocreuxia/Sisyranthus nk;clade, from which the core Ceropegieae are derived. The four Ceropegia species included are not monophyletic, and their relationship to Brachystelma changes depending on the marker studied. The stem succulent taxa fall in a number of well supported, but unresolved clades, the most prominent being the predominantly southern African clade comprising Orbea, Stapelia and some other genera. The most derived taxa of NE Africa, Duvaliandra and White-sloanea, are basal to this southern African clade. The other clades comprise the more basal genera of stem-succulent stapeliads, including the members of the Caralluma complex. Of the 17 genera accepted by Plowes for the Caralluma complex, seven are recognized: Caralluma, Apteranthes, Australluma, Boucerosia, Caudanthera, Desmidorchis and Monolluma. New combinations are proposed in 15 cases; Caralluma adscendens var. geniculata is raised to specific rank. Anomalluma is reinstated, and Pseudolithos mccoyi is transfered to it. A broadened concept for Orbea (incl. Angolluma and Orbeopsis) is recognized, but Orbeanthus is kept separate. The monotypic Ballyanthus, recently separated from Orbea, is nested within Duvalia. Piaranthus (incl. Huerniopsis) is monophyletic. The bitypic Notechidnopsis is reduced to the type species, N. tessellata, while N. columnaris is transferred to a new genus, Richtersveldia.
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An ethnobotanical research was carried out in Makran (Southern Pakistan) as a part of an Italian archaeological, historical and environmental Mission. 27 medicinal plants, used by local people, were identified and listed; information on their traditional medicinal uses is reported and discussed.
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Objectives Caralluma is a xerophytic genus used as traditional medicine for the treatment of diabetes, inflammation, leprosy, obesity and rheumatism. Objectives of this review are to establish a relationship between traditional uses and scientific studies by critically evaluating the available fragmented literature on ethnobotany, pharmacology, phytochemistry and toxicology of genus Caralluma.Key findingsEthnomedical uses of Caralluma have been recorded from various countries such as China, India, Iran and Pakistan for six major classes of diseases including diabetes and gastrointestinal disorders. This review indicated the efficacy of genus Caralluma in several in vitro and in vivo pharmacological properties such as antimicrobial, antioxidant and anticancer activity. These bioactivity might be due to the presence of certain classes of compounds in genus Caralluma including pregnane glycosides, flavonoid glycosides and flavones.SummaryTraditional uses and scientific evaluation of Caralluma indicates that it is one of the most widely used genus in some parts of the world. Further studies on the structural activity relationship of some of the isolated compound may improve their biological potency as well as scientific exploitation of traditional uses of the genus.
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Twenty new pregnane glycosides were isolated from the whole plant of Caralluma negevensis. Their structures were elucidated by extensive spectroscopic methods including 1D-(1H, 13C, 13C DEPT, TOCSY, ROESY) and 2D-NMR experiments (DQF-COSY, HSQC, HMBC, HOHAHA) as well as ESI-MS analysis. Pregnane glycosides were tested for their cytotoxic and genotoxic activity. © 2002 Elsevier Science Ltd. All rights reserved.
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